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dsRNA formation leads to preferential nuclear export and gene expression
Nature ( IF 50.5 ) Pub Date : 2024-06-19 , DOI: 10.1038/s41586-024-07576-w
Ivo Coban , Jan-Philipp Lamping , Anna Greta Hirsch , Sarah Wasilewski , Orr Shomroni , Oliver Giesbrecht , Gabriela Salinas , Heike Krebber

When mRNAs have been transcribed and processed in the nucleus, they are exported to the cytoplasm for translation. This export is mediated by the export receptor heterodimer Mex67–Mtr2 in the yeast Saccharomyces cerevisiae (TAP–p15 in humans)1,2. Interestingly, many long non-coding RNAs (lncRNAs) also leave the nucleus but it is currently unclear why they move to the cytoplasm3. Here we show that antisense RNAs (asRNAs) accelerate mRNA export by annealing with their sense counterparts through the helicase Dbp2. These double-stranded RNAs (dsRNAs) dominate export compared with single-stranded RNAs (ssRNAs) because they have a higher capacity and affinity for the export receptor Mex67. In this way, asRNAs boost gene expression, which is beneficial for cells. This is particularly important when the expression program changes. Consequently, the degradation of dsRNA, or the prevention of its formation, is toxic for cells. This mechanism illuminates the general cellular occurrence of asRNAs and explains their nuclear export.



中文翻译:


dsRNA 形成导致优先核输出和基因表达



当 mRNA 在细胞核中转录和加工后,它们被输出到细胞质进行翻译。这种输出是由酿酒酵母中的输出受体异二聚体 Mex67–Mtr2(人类中的 TAP–p15) 1,2 介导的。有趣的是,许多长链非编码RNA(lncRNA)也离开细胞核,但目前尚不清楚它们为何移动到细胞质 3 。在这里,我们展示了反义 RNA (asRNA) 通过解旋酶 Dbp2 与其正义对应物退火,从而加速 mRNA 输出。与单链 RNA (ssRNA) 相比,这些双链 RNA (dsRNA) 在输出中占主导地位,因为它们对输出受体 Mex67 具有更高的容量和亲和力。通过这种方式,asRNA 可以促进基因表达,这对细胞有益。当表达程序发生变化时,这一点尤其重要。因此,dsRNA 的降解或阻止其形成对细胞来说是有毒的。这种机制阐明了 asRNA 的一般细胞发生情况并解释了它们的核输出。

更新日期:2024-06-20
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