The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long noncoding RNA (lncRNA) has key roles in regulating transcription, splicing, tumorigenesis, etc. Its maturation and stabilization require precise processing by RNase P, which simultaneously initiates the biogenesis of a 3′ cytoplasmic MALAT1-associated small cytoplasmic RNA (mascRNA). mascRNA was proposed to fold into a transfer RNA (tRNA)-like secondary structure but lacks eight conserved linking residues required by the canonical tRNA fold. Here we report crystal structures of human mascRNA before and after processing, which reveal an ultracompact, quasi-tRNA-like structure. Despite lacking all linker residues, mascRNA faithfully recreates the characteristic ‘elbow’ feature of tRNAs to recruit RNase P and ElaC homolog protein 2 (ELAC2) for processing, which exhibit distinct substrate specificities. Rotation and repositioning of the D-stem and anticodon regions preclude mascRNA from aminoacylation, avoiding interference with translation. Therefore, a class of metazoan lncRNA loci uses a previously unrecognized, unusually streamlined quasi-tRNA architecture to recruit select tRNA-processing enzymes while excluding others to drive bespoke RNA biogenesis, processing and maturation.

转移相关肺腺癌转录本 1 （MALAT1） 长链非编码 RNA （lncRNA） 在调节转录、剪接、肿瘤发生等方面具有关键作用。它的成熟和稳定需要 RNase P 的精确加工，RNase P 同时启动 3' 细胞质 MALAT1 相关小细胞质 RNA （mascRNA） 的生物发生。mascRNA 被提议折叠成转移 RNA （tRNA） 样二级结构，但缺乏经典 tRNA 折叠所需的 8 个保守连接残基。在这里，我们报告了加工前后人类 mascRNA 的晶体结构，揭示了超紧凑的准 tRNA 样结构。尽管缺乏所有接头残基，但 mascRNA 忠实地再现了 tRNA 的特征性“肘部”特征，以募集 RNase P 和 ElaC 同源物蛋白 2 （ELAC2） 进行加工，它们表现出不同的底物特异性。D 茎和反密码子区域的旋转和重新定位阻止了 mascRNA 的氨酰化，避免了对翻译的干扰。因此，一类后生动物 lncRNA 位点使用以前未识别的、异常简化的准 tRNA 结构来募集选定的 tRNA 加工酶，同时排除其他酶来驱动定制的 RNA 生物发生、加工和成熟。