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N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis Genome Biol. (IF 10.1) Pub Date : 2024-07-19 Qian Ma, Yiqian Gui, Xixiang Ma, Bingqian Zhang, Wenjing Xiong, Shiyu Yang, Congcong Cao, Shaomei Mo, Ge Shu, Jing Ye, Kuan Liu, Xiaoli Wang, Yaoting Gui, Fengli Wang, Shuiqiao Yuan
The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional
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A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data Genome Biol. (IF 10.1) Pub Date : 2024-07-19 Alessandro Vinceti, Raffaele M. Iannuzzi, Isabella Boyle, Lucia Trastulla, Catarina D. Campbell, Francisca Vazquez, Joshua M. Dempster, Francesco Iorio
CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias). More worryingly, proximal targeted loci tend to
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Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Farhia Kabeer, Hoa Tran, Mirela Andronescu, Gurdeep Singh, Hakwoo Lee, Sohrab Salehi, Beixi Wang, Justina Biele, Jazmine Brimhall, David Gee, Viviana Cerda, Ciara O’Flanagan, Teresa Algara, Takako Kono, Sean Beatty, Elena Zaikova, Daniel Lai, Eric Lee, Richard Moore, Andrew J. Mungall, Marc J. Williams, Andrew Roth, Kieran R. Campbell, Sohrab P. Shah, Samuel Aparicio
The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy
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Non-coding variants impact cis-regulatory coordination in a cell type-specific manner Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Olga Pushkarev, Guido van Mierlo, Judith Franziska Kribelbauer, Wouter Saelens, Vincent Gardeux, Bart Deplancke
Interactions among cis-regulatory elements (CREs) play a crucial role in gene regulation. Various approaches have been developed to map these interactions genome-wide, including those relying on interindividual epigenomic variation to identify groups of covariable regulatory elements, referred to as chromatin modules (CMs). While CM mapping allows to investigate the relationship between chromatin modularity
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Leveraging neighborhood representations of single-cell data to achieve sensitive DE testing with miloDE Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Alsu Missarova, Emma Dann, Leah Rosen, Rahul Satija, John Marioni
Single-cell RNA-sequencing enables testing for differential expression (DE) between conditions at a cell type level. While powerful, one of the limitations of such approaches is that the sensitivity of DE testing is dictated by the sensitivity of clustering, which is often suboptimal. To overcome this, we present miloDE—a cluster-free framework for DE testing (available as an open-source R package)
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Graph-based self-supervised learning for repeat detection in metagenomic assembly Genome Res. (IF 6.2) Pub Date : 2024-07-19 Ali Azizpour, Advait Balaji, Todd J. Treangen, Santiago Segarra
Repetitive DNA (repeats) poses significant challenges for accurate and efficient genome assembly and sequence alignment. This is particularly true for metagenomic data, where genome dynamics such as horizontal gene transfer, gene duplication, and gene loss/gain complicate accurate genome assembly from metagenomic communities. Detecting repeats is a crucial first step in overcoming these challenges
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Sampling globally and locally correct RNA 3D structures using Ernwin, SPQR and experimental SAXS data Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-18 Bernhard C Thiel, Giovanni Bussi, Simón Poblete, Ivo L Hofacker
The determination of the three-dimensional structure of large RNA macromolecules in solution is a challenging task that often requires the use of several experimental and computational techniques. Small-angle X-ray scattering can provide insight into some geometrical properties of the probed molecule, but this data must be properly interpreted in order to generate a three-dimensional model. Here, we
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DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-18 Lavernchy Jovanska, I-Chen Lin, Jhong-Syuan Yao, Chia-Ling Chen, Hou-Cheng Liu, Wan-Chen Li, Yu-Chien Chuang, Chi-Ning Chuang, Albert Chen-Hsin Yu, Hsin-Nan Lin, Wen-Li Pong, Chang-I Yu, Ching-Yuan Su, Yi-Ping Chen, Ruey-Shyang Chen, Yi-Ping Hsueh, Hanna S Yuan, Ljudmilla Timofejeva, Ting-Fang Wang
Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type
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Differential processing of RNA polymerase II at DNA damage correlates with transcription-coupled repair syndrome severity Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-18 Camila Gonzalo-Hansen, Barbara Steurer, Roel C Janssens, Di Zhou, Marjolein van Sluis, Hannes Lans, Jurgen A Marteijn
DNA damage severely impedes gene transcription by RNA polymerase II (Pol II), causing cellular dysfunction. Transcription-Coupled Nucleotide Excision Repair (TC-NER) specifically removes such transcription-blocking damage. TC-NER initiation relies on the CSB, CSA and UVSSA proteins; loss of any results in complete TC-NER deficiency. Strikingly, UVSSA deficiency results in UV-Sensitive Syndrome (UVSS)
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Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer Nat. Genet. (IF 31.7) Pub Date : 2024-07-17 Shuang G. Zhao, Matthew Bootsma, Stanley Zhou, Raunak Shrestha, Thaidy Moreno-Rodriguez, Arian Lundberg, Chu Pan, Christopher Arlidge, James R. Hawley, Adam Foye, Alana S. Weinstein, Martin Sjöström, Meng Zhang, Haolong Li, Lisa N. Chesner, Nicholas R. Rydzewski, Kyle T. Helzer, Yue Shi, Molly Lynch, Scott M. Dehm, Joshua M. Lang, Joshi J. Alumkal, Hansen H. He, Alexander W. Wyatt, Rahul Aggarwal,
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Haplotype-aware sequence alignment to pangenome graphs Genome Res. (IF 6.2) Pub Date : 2024-07-16 Ghanshyam Chandra, Daniel Gibney, Chirag Jain
Modern pangenome graphs are built using haplotype-resolved genome assemblies. When mapping reads to a pangenome graph, prioritizing alignments that are consistent with the known haplotypes improves genotyping accuracy. However, the existing rigorous formulations for co-linear chaining and alignment problems do not consider the haplotype paths in a pangenome graph. This often leads to spurious read
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High-fidelity, large-scale targeted profiling of microsatellites Genome Res. (IF 6.2) Pub Date : 2024-07-16 Caitlin A Loh, Danielle A Shields, Adam Schwing, Gilad D Evrony
Microsatellites are highly mutable sequences that can serve as markers for relationships among individuals or cells within a population. The accuracy and resolution of reconstructing these relationships depends on the fidelity of microsatellite profiling and the number of microsatellites profiled. However, current methods for targeted profiling of microsatellites incur significant "stutter" artifacts
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CLOCI: unveiling cryptic fungal gene clusters with generalized detection Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-17 Zachary Konkel, Laura Kubatko, Jason C Slot
Gene clusters are genomic loci that contain multiple genes that are functionally and genetically linked. Gene clusters collectively encode diverse functions, including small molecule biosynthesis, nutrient assimilation, metabolite degradation, and production of proteins essential for growth and development. Identifying gene clusters is a powerful tool for small molecule discovery and provides insight
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Instability throughout the Saccharomyces cerevisiae genome resulting from Pms1 endonuclease deficiency Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-17 Scott A Lujan, Marta A Garbacz, Sascha E Liberti, Adam B Burkholder, Thomas A Kunkel
The endonuclease activity of Pms1 directs mismatch repair by generating a nick in the newly replicated DNA strand. Inactivating Pms2, the human homologue of yeast Pms1, increases the chances of colorectal and uterine cancers. Here we use whole genome sequencing to show that loss of this endonuclease activity, via the pms1-DE variant, results in strong mutator effects throughout the Saccharomyces cerevisiae
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Understanding X chromosome loss Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Safia Danovi
Mosaic loss of one copy of the X chromosome (mLOX) occurs more frequently in female individuals than loss of autosomes. It preferentially affects the inactivated chromosome and is associated with an increased risk of leukemia. To discover its genetic drivers, Liu et al. performed an epidemiological and genetic meta-analysis of 883,574 female participants from 8 biobanks from Europe and East Asia. They
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A one-stop shop for 3D spatial transcriptomics Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Tiago Faial
Spatial transcriptomic methods are developing rapidly and will undoubtedly facilitate the gain of new insights into both homeostatic and disease mechanisms. However, there are numerous challenges associated with them, including implementation, scaling, cost, and data resolution and interpretation. To address these issues, Schott et al. developed Open-ST, an open-source sequencing-based experimental
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Measuring nascent transcription in single cells Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Chiara Anania
Single-cell transcriptomic technologies enable the profiling of gene expression in individual cells but lack the ability to measure nascent transcription. This caveat hinders a precise understanding of the timing and mechanistic underpinnings of transcriptional dynamics. To address this limitation, Mahat et al. developed a global run-on sequencing (GRO-seq) method that uses click chemistry to barcode
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Finding cancer mutagens using signature analysis Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Michael Fletcher
Tumor somatic mutational signatures offer insights into disease etiology, and such analyses may identify exposures underlying differential cancer incidence between countries. Past work on esophageal cancer did not find major mutational differences, in contrast with a new study by Senkin et al. on clear cell renal carcinoma. Whole-genome sequencing was carried out on 962 clear cell renal carcinomas
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Single-cell discovery of m6A RNA modifications in the hippocampus Genome Res. (IF 6.2) Pub Date : 2024-07-15 Shuangshuang Feng, Maitena Tellaetxe-Abete, Yujie Zhang, Yan Peng, Han Zhou, Mingjie Dong, Erika Larrea, Liang Xue, Li Zhang, Magdalena J. Koziol
N6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing
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GSearch: ultra-fast and scalable genome search by combining K-mer hashing with hierarchical navigable small world graphs Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Jianshu Zhao, Jean Pierre Both, Luis M Rodriguez-R, Konstantinos T Konstantinidis
Genome search and/or classification typically involves finding the best-match database (reference) genomes and has become increasingly challenging due to the growing number of available database genomes and the fact that traditional methods do not scale well with large databases. By combining k-mer hashing-based probabilistic data structures (i.e. ProbMinHash, SuperMinHash, Densified MinHash and SetSketch)
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Adenovirus small E1A directs activation of Alu transcription at YAP/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodeler Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Simona Cantarella, Marco Vezzoli, Davide Carnevali, Marco Morselli, Nathan R Zemke, Barbara Montanini, Coralie F Daussy, Harald Wodrich, Martin Teichmann, Matteo Pellegrini, Arnold J Berk, Giorgio Dieci, Roberto Ferrari
Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types
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Analysis of bacterial transcriptome and epitranscriptome using nanopore direct RNA sequencing Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Lu Tan, Zhihao Guo, Yanwen Shao, Lianwei Ye, Miaomiao Wang, Xin Deng, Sheng Chen, Runsheng Li
Bacterial gene expression is a complex process involving extensive regulatory mechanisms. Along with growing interests in this field, Nanopore Direct RNA Sequencing (DRS) provides a promising platform for rapid and comprehensive characterization of bacterial RNA biology. However, the DRS of bacterial RNA is currently deficient in the yield of mRNA-mapping reads and has yet to be exploited for transcriptome-wide
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The critical role of the iron–sulfur cluster and CTC components in DOG-1/BRIP1 function in Caenorhabditis elegans Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Xiao Li, Ivette Maria Menendez Perdomo, Victoria Rodrigues Alves Barbosa, Catherine Diao, Maja Tarailo-Graovac
FANCJ/BRIP1, initially identified as DOG-1 (Deletions Of G-rich DNA) in Caenorhabditis elegans, plays a critical role in genome integrity by facilitating DNA interstrand cross-link repair and resolving G-quadruplex structures. Its function is tightly linked to a conserved [4Fe–4S] cluster-binding motif, mutations of which contribute to Fanconi anemia and various cancers. This study investigates the
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Rapid functional activation of horizontally transferred eukaryotic intron-containing genes in the bacterial recipient Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Wen Yuan, Jing Yu, Zhichao Li
Horizontal gene transfer has occurred across all domains of life and contributed substantially to the evolution of both prokaryotes and eukaryotes. Previous studies suggest that many horizontally transferred eukaryotic genes conferred selective advantages to bacterial recipients, but how these eukaryotic genes evolved into functional bacterial genes remained unclear, particularly how bacteria overcome
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Trypanosome mRNA recapping is triggered by hypermethylation originating from cap 4 Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Anna V Ignatochkina, Jesavel A Iguchi, Anilkumar R Kore, C Kiong Ho
RNA methylation adjacent to the 5′ cap plays a critical role in controlling mRNA stability and protein synthesis. In trypanosomes the 5′-terminus of mRNA is protected by hypermethylated cap 4. Trypanosomes encode a cytoplasmic recapping enzyme TbCe1 which possesses an RNA kinase and guanylyltransferase activities that can convert decapped 5′-monophosphate-terminated pRNA into GpppRNA. Here, we demonstrated
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Re-engineered guide RNA enables DNA loops and contacts modulating repression in E. coli Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Yunshi Yang, Iris Rocamonde-Lago, Boxuan Shen, Ieva Berzina, Johanna Zipf, Björn Högberg
RNA serves as information media as well as molecular scaffold in nature and synthetic systems. The single guide RNA (sgRNA) widely applied in CRISPR techniques exemplifies both functions, with a guide region bearing DNA base-pairing information, and a structural motif for Cas9 protein scaffolding. The scaffold region has been modified by fusing RNA aptamers to the tetra-stem loop. The guide region
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SigAlign: an alignment algorithm guided by explicit similarity criteria Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Kunhyung Bahk, Joohon Sung
In biological sequence alignment, prevailing heuristic aligners achieve high-throughput by several approximation techniques, but at the cost of sacrificing the clarity of output criteria and creating complex parameter spaces. To surmount these challenges, we introduce ‘SigAlign’, a novel alignment algorithm that employs two explicit cutoffs for the results: minimum length and maximum penalty per length
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mRNA-specific readthrough of nonsense codons by antisense oligonucleotides (R-ASOs) Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Denis Susorov, Dimas Echeverria, Anastasia Khvorova, Andrei A Korostelev
Nonsense mutations account for >10% of human genetic disorders, including cystic fibrosis, Alagille syndrome, and Duchenne muscular dystrophy. A nonsense mutation results in the expression of a truncated protein, and therapeutic strategies aim to restore full-length protein expression. Most strategies under development, including small-molecule aminoglycosides, suppressor tRNAs, or the targeted degradation
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Single-mode termination of phage transcriptions, disclosing bacterial adaptation for facilitated reinitiations Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Eunho Song, Sun Han, Heesoo Uhm, Changwon Kang, Sungchul Hohng
Bacterial and bacteriophage RNA polymerases (RNAPs) have divergently evolved and share the RNA hairpin-dependent intrinsic termination of transcription. Here, we examined phage T7, T3 and SP6 RNAP terminations utilizing the single-molecule fluorescence assays we had developed for bacterial terminations. We discovered the phage termination mode or outcome is virtually single with decomposing termination
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The RNA helicase DDX39 contributes to the nuclear export of spliceosomal U snRNA by loading of PHAX onto RNA Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Ichiro Taniguchi, Tetsuro Hirose, Mutsuhito Ohno
RNA helicases are involved in RNA metabolism in an ATP-dependent manner. Although many RNA helicases unwind the RNA structure and/or remove proteins from the RNA, some can load their interacting proteins onto RNAs. Here, we developed an in vitro strategy to identify the ATP-dependent factors involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export. We identified the RNA helicase UAP56/DDX39B
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A new approach to RNA synthesis: immobilization of stably and functionally co-tethered promoter DNA and T7 RNA polymerase Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Kithmie MalagodaPathiranage, Ruptanu Banerjee, Craig T Martin
Current approaches to RNA synthesis/manufacturing require substantial (and incomplete) purification post-synthesis. We have previously demonstrated the synthesis of RNA from a complex in which T7 RNA polymerase is tethered to promoter DNA. In the current work, we extend this approach to demonstrate an extremely stable system of functional co-tethered complex to a solid support. Using the system attached
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Improving estimates of loss-of-function constraint for short genes Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Nicola Whiffin
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Comprehensive and deep evaluation of structural variation detection pipelines with third-generation sequencing data Genome Biol. (IF 10.1) Pub Date : 2024-07-15 Zhi Liu, Zhi Xie, Miaoxin Li
Structural variation (SV) detection methods using third-generation sequencing data are widely employed, yet accurately detecting SVs remains challenging. Different methods often yield inconsistent results for certain SV types, complicating tool selection and revealing biases in detection. This study comprehensively evaluates 53 SV detection pipelines using simulated and real data from PacBio (CLR:
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Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans Genome Biol. (IF 10.1) Pub Date : 2024-07-15 Wen-Jou Chang, Maria S. Baker, Eleonora Laritsky, Chathura J. Gunasekara, Uditha Maduranga, Justine C. Galliou, Joseph W. McFadden, Jessica R. Waltemyer, Bruce Berggren-Thomas, Brianna N. Tate, Hanxue Zhang, Benjamin D. Rosen, Curtis P. Van Tassell, George E. Liu, Cristian Coarfa, Yi Athena Ren, Robert A. Waterland
We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences
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Programmable DNA rearrangements using bridge RNAs Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-07-12 Henry Ertl
Two studies in Nature reveal the mechanistic and structural properties of a family of mobile genetic elements that can be reprogrammed to engineer genome modifications.
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SMCHD1 activates the expression of genes required for the expansion of human myoblasts Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-12 Matthew Man-Kin Wong, Sarah Hachmer, Ed Gardner, Valeria Runfola, Eric Arezza, Lynn A Megeney, Charles P Emerson, Davide Gabellini, F Jeffrey Dilworth
SMCHD1 is an epigenetic regulatory protein known to modulate the targeted repression of large chromatin domains. Diminished SMCHD1 function in muscle fibers causes Facioscapulohumeral Muscular Dystrophy (FSHD2) through derepression of the D4Z4 chromatin domain, an event which permits the aberrant expression of the disease-causing gene DUX4. Given that SMCHD1 plays a broader role in establishing the
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Conformational dynamics of CasX (Cas12e) in mediating DNA cleavage revealed by single-molecule FRET Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-12 Wenjing Xing, Danyuan Li, Wenjuan Wang, Jun-Jie Gogo Liu, Chunlai Chen
CasX (also known as Cas12e), a Class 2 CRISPR-Cas system, shows promise in genome editing due to its smaller size compared to the widely used Cas9 and Cas12a. Although the structures of CasX–sgRNA–DNA ternary complexes have been resolved and uncover a distinctive NTSB domain, the dynamic behaviors of CasX are not well characterized. In this study, we employed single-molecule and biochemical assays
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High resolution landscape of ribosomal RNA processing and surveillance Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-12 Weidong An, Yunxiao Yan, Keqiong Ye
Ribosomal RNAs are processed in a complex pathway. We profiled rRNA processing intermediates in yeast at single-molecule and single-nucleotide levels with circularization, targeted amplification and deep sequencing (CircTA-seq), gaining significant mechanistic insights into rRNA processing and surveillance. The long form of the 5′ end of 5.8S rRNA is converted to the short form and represents an intermediate
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Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-12 Vivian Lobo, Iwona Nowak, Carola Fernandez, Ana Iris Correa Muler, Jakub O Westholm, Hsiang-Chi Huang, Ivo Fabrik, Hang T Huynh, Evgeniia Shcherbinina, Melis Poyraz, Anetta Härtlova, Daniel Benhalevy, Davide Angeletti, Aishe A Sarshad
In mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx
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Cas9 interaction with the tracrRNA nexus modulates the repression of type II-A CRISPR-cas genes Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-12 Hyejin Kim, Luciano A Marraffini
Immune responses need to be regulated to prevent autoimmunity. CRISPR-Cas systems provide adaptive immunity in prokaryotes through the acquisition of short DNA sequences from invading viruses (bacteriophages), known as spacers. Spacers are inserted into the CRISPR locus and serve as templates for the transcription of guides used by RNA-guided nucleases to recognize complementary nucleic acids of the
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EcCas6e-based antisense crRNA for gene repression and RNA editing in microorganisms Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-12 Mutong Li, Zhaohui Cai, Shucheng Song, Xinmin Yue, Wenyu Lu, Shuquan Rao, Chuanbo Zhang, Chaoyou Xue
Precise gene regulation and programmable RNA editing are vital RNA-level regulatory mechanisms. Gene repression tools grounded in small non-coding RNAs, microRNAs, and CRISPR-dCas proteins, along with RNA editing tools anchored in Adenosine Deaminases acting on RNA (ADARs), have found extensive application in molecular biology and cellular engineering. Here, we introduced a novel approach wherein we
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DEAD box RNA helicases are pervasive protein kinase interactors and activators Genome Res. (IF 6.2) Pub Date : 2024-07-10 Alexander Hirth, Edoardo Fatti, Eugen Netz, Sergio P. Acebron, Dimitris Papageorgiou, Andrea Švorinić, Cristina-Maria Cruciat, Emil Karaulanov, Alexandr Gopanenko, Tianheng Zhu, Irmgard Sinning, Jeroen Krijgsveld, Oliver Kohlbacher, Christof Niehrs
DEAD box (DDX) RNA helicases are a large family of ATPases, many of which have unknown functions. There is emerging evidence that besides their role in RNA biology, DDX proteins may stimulate protein kinases. To investigate if protein kinase–DDX interaction is a more widespread phenomenon, we conducted three orthogonal large-scale screens, including proteomics analysis with 32 RNA helicases, protein
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Accurate allocation of multimapped reads enables regulatory element analysis at repeats Genome Res. (IF 6.2) Pub Date : 2024-07-10 Alexis Morrissey, Jeffrey Shi, Daniela Q. James, Shaun Mahony
Transposable elements (TEs) and other repetitive regions have been shown to contain gene regulatory elements, including transcription factor binding sites. However, regulatory elements harbored by repeats have proven difficult to characterize using short-read sequencing assays such as ChIP-seq or ATAC-seq. Most regulatory genomics analysis pipelines discard “multimapped” reads that align equally well
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Structural basis of water-mediated cis Watson–Crick/Hoogsteen base-pair formation in non-CpG methylation Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Shan-Meng Lin, Hsiang-Ti Huang, Pei-Ju Fang, Chi-Fon Chang, Roshan Satange, Chung-ke Chang, Shan-Ho Chou, Stephen Neidle, Ming-Hon Hou
Non-CpG methylation is associated with several cellular processes, especially neuronal development and cancer, while its effect on DNA structure remains unclear. We have determined the crystal structures of DNA duplexes containing -CGCCG- regions as CCG repeat motifs that comprise a non-CpG site with or without cytosine methylation. Crystal structure analyses have revealed that the mC:G base-pair can
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Partial wrapping of single-stranded DNA by replication protein A and modulation through phosphorylation Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Rahul Chadda, Vikas Kaushik, Iram Munir Ahmad, Jaigeeth Deveryshetty, Alex S Holehouse, Snorri Th Sigurdsson, Gargi Biswas, Yaakov Levy, Brian Bothner, Richard B Cooley, Ryan A Mehl, Reza Dastvan, Sofia Origanti, Edwin Antony
Single-stranded DNA (ssDNA) intermediates which emerge during DNA metabolic processes are shielded by replication protein A (RPA). RPA binds to ssDNA and acts as a gatekeeper to direct the ssDNA towards downstream DNA metabolic pathways with exceptional specificity. Understanding the mechanistic basis for such RPA-dependent functional specificity requires knowledge of the structural conformation of
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Molecular basis for cA6 synthesis by a type III-A CRISPR–Cas enzyme and its conversion to cA4 production Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Hemant N Goswami, Fozieh Ahmadizadeh, Bing Wang, Doreen Addo-Yobo, Yu Zhao, A Carl Whittington, Huan He, Michael P Terns, Hong Li
The type III-A (Csm) CRISPR–Cas systems are multi-subunit and multipronged prokaryotic enzymes in guarding the hosts against viral invaders. Beyond cleaving activator RNA transcripts, Csm confers two additional activities: shredding single-stranded DNA and synthesizing cyclic oligoadenylates (cOAs) by the Cas10 subunit. Known Cas10 enzymes exhibit a fascinating diversity in cOA production. Three major
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tRNA expression and modification landscapes, and their dynamics during zebrafish embryo development Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Tom Rappol, Maria Waldl, Anastasia Chugunova, Ivo L Hofacker, Andrea Pauli, Elisa Vilardo
tRNA genes exist in multiple copies in the genome of all organisms across the three domains of life. Besides the sequence differences across tRNA copies, extensive post-transcriptional modification adds a further layer to tRNA diversification. Whilst the crucial role of tRNAs as adapter molecules in protein translation is well established, whether all tRNAs are actually expressed, and whether the differences
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BOD1L mediates chromatin binding and non-canonical function of H3K4 methyltransferase SETD1A Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Takayuki Hoshii, Sota Kikuchi, Tomoya Kujirai, Takeshi Masuda, Tomoko Ito, Satoshi Yasuda, Makoto Matsumoto, Bahityar Rahmutulla, Masaki Fukuyo, Takeshi Murata, Hitoshi Kurumizaka, Atsushi Kaneda
The H3K4 methyltransferase SETD1A plays an essential role in both development and cancer. However, essential components involved in SETD1A chromatin binding remain unclear. Here, we discovered that BOD1L exhibits the highest correlated SETD1A co-dependency in human cancer cell lines. BOD1L knockout reduces leukemia cells in vitro and in vivo, and mimics the transcriptional profiles observed in SETD1A
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Ocr-mediated suppression of BrxX unveils a phage counter-defense mechanism Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Shen Li, Tianhao Xu, Xinru Meng, Yujuan Yan, Ying Zhou, Lei Duan, Yulong Tang, Li Zhu, Litao Sun
The burgeoning crisis of antibiotic resistance has directed attention to bacteriophages as natural antibacterial agents capable of circumventing bacterial defenses. Central to this are the bacterial defense mechanisms, such as the BREX system, which utilizes the methyltransferase BrxX to protect against phage infection. This study presents the first in vitro characterization of BrxX from Escherichia
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CyCoNP lncRNA establishes cis and trans RNA–RNA interactions to supervise neuron physiology Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Fabio Desideri, Alessandro Grazzi, Michela Lisi, Adriano Setti, Tiziana Santini, Alessio Colantoni, Gabriele Proietti, Andrea Carvelli, Gian Gaetano Tartaglia, Monica Ballarino, Irene Bozzoni
The combination of morphogenetic and transcription factors together with the synergic aid of noncoding RNAs and their cognate RNA binding proteins contribute to shape motor neurons (MN) identity. Here, we extend the noncoding perspective of human MN, by detailing the molecular and biological activity of CyCoNP (as Cytoplasmic Coordinator of Neural Progenitors) a highly expressed and MN-enriched human
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Weak-cooperative binding of a long single-stranded DNA chain on a surface Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-11 Giovanni Nava, Thomas Carzaniga, Luca Casiraghi, Erik Bot, Giuliano Zanchetta, Francesco Damin, Marcella Chiari, Gerald Weber, Tommaso Bellini, Luca Mollica, Marco Buscaglia
Binding gene-wide single-stranded nucleic acids to surface-immobilized complementary probes is an important but challenging process for biophysical studies and diagnostic applications. The challenge comes from the conformational dynamics of the long chain that affects its accessibility and weakens its hybridization to the probes. We investigated the binding of bacteriophage genome M13mp18 on several
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TFscope: systematic analysis of the sequence features involved in the binding preferences of transcription factors Genome Biol. (IF 10.1) Pub Date : 2024-07-10 Raphaël Romero, Christophe Menichelli, Christophe Vroland, Jean-Michel Marin, Sophie Lèbre, Charles-Henri Lecellier, Laurent Bréhélin
Characterizing the binding preferences of transcription factors (TFs) in different cell types and conditions is key to understand how they orchestrate gene expression. Here, we develop TFscope, a machine learning approach that identifies sequence features explaining the binding differences observed between two ChIP-seq experiments targeting either the same TF in two conditions or two TFs with similar
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sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden Genome Biol. (IF 10.1) Pub Date : 2024-07-10 Sonia N. Acharya, Ruth V. Nichols, Lauren E. Rylaarsdam, Brendan L. O’Connell, Theodore P. Braun, Andrew C. Adey
DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per
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CoRAL accurately resolves extrachromosomal DNA genome structures with long-read sequencing Genome Res. (IF 6.2) Pub Date : 2024-07-09 Kaiyuan Zhu, Matthew Gregory Jones, Jens Luebeck, Xinxin Bu, Hyerim Yi, King L. Huang, Ivy Tsz-Lo Wong, Shu Zhang, Paul S. Mischel, Howard Chang, Vineet Bafna
Extrachromosomal DNA (ecDNA) is a central mechanism for focal oncogene amplification in cancer, occurring in approximately 15% of early-stage cancers and 30% of late-stage cancers. EcDNAs drive tumor formation, evolution, and drug resistance by dynamically modulating oncogene copy-number and rewiring gene-regulatory networks. Elucidating the genomic architecture of ecDNA amplifications is critical
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Accurate estimation of pathway activity in single cells for clustering and differential analysis Genome Res. (IF 6.2) Pub Date : 2024-07-09 Daniel Davis, Avishai Wizel, Yotam Drier
Inferring which and how biological pathways and gene sets change is a key question in many studies that utilize single-cell RNA sequencing. Typically, these questions are addressed by quantifying the enrichment of known gene sets in lists of genes derived from global analysis. Here we offer SiPSiC, a new method to infer pathway activity in every single cell. This allows more sensitive differential
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Decoding protein–RNA interactions using CLIP-based methodologies Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-07-09 Joy S. Xiang, Danielle M. Schafer, Katherine L. Rothamel, Gene W. Yeo
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Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue Genome Res. (IF 6.2) Pub Date : 2024-07-08 Aarthi Venkat, Maximillian J. Carlino, Betty R. Lawton, Manju L. Prasad, Matthew Amodio, Courtney E. Gibson, Caroline J. Zeiss, Scott E. Youlten, Smita Krishnaswamy, Diane S. Krause
Studies on human parathyroids are generally limited to hyperfunctioning glands owing to the difficulty in obtaining normal human tissue. We therefore obtained non-human primate (NHP) parathyroids to provide a suitable alternative for sequencing that would bear a close semblance to human organs. Single-cell RNA expression analysis of parathyroids from four healthy adult M. mulatta reveals a continuous
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Large-scale investigation of species-specific orphan genes in the human gut microbiome elucidates their evolutionary origins Genome Res. (IF 6.2) Pub Date : 2024-07-08 Nikolaos Vakirlis, Anne Kupczok
Species-specific genes, also known as orphans, are ubiquitous across life's domains. In prokaryotes, species-specific orphan genes (SSOGs) are mostly thought to originate in external elements such as viruses followed by horizontal gene transfer, whereas the scenario of native origination, through rapid divergence or de novo, is mostly dismissed. However, quantitative evidence supporting either scenario
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Comparative genomics of Cryptosporidium parvum reveals the emergence of an outbreak-associated population in Europe and its spread to the United States Genome Res. (IF 6.2) Pub Date : 2024-07-08 Greta Bellinzona, Tiago Nardi, Michele Castelli, Gherard Batisti Biffignandi, Karim Adjou, Martha Betson, Yannick Blanchard, Ioana Bujila, Rachel Chalmers, Rebecca Davidson, Nicoletta D'Avino, Tuulia Enbom, Jacinto Gomes, Gregory Karadjian, Christian Klotz, Emma Östlund, Judith Plutzer, Ruska Rimhanen-Finne, Guy Robinson, Anna Rosa Sannella, Jacek Sroka, Christen Rune Stensvold, Karin Troell, Paolo
The zoonotic parasite Cryptosporidium parvum is a global cause of gastrointestinal disease in humans and ruminants. Sequence analysis of the highly polymorphic gp60 gene enabled the classification of C. parvum isolates into multiple groups (e.g., IIa, IIc, Id) and a large number of subtypes. In Europe, subtype IIaA15G2R1 is largely predominant and has been associated with many water- and food-borne