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物 1 (MALAT1) 长非编码 RNA (lncRNA) 在调节转录、剪接、肿瘤发生等方面发挥着关键作用。其成熟和稳定需要 RNase P 的精确处理，同时启动 3' 的生物发生。细胞质 MALAT1 相关小细胞质 RNA (mascRNA)。 mascRNA 被提议折叠成类似转移 RNA (tRNA) 的二级结构，但缺乏典型 tRNA 折叠所需的八个保守连接残基。在这里，我们报告了处理前后人类 mascRNA 的晶体结构，揭示了超紧凑的类 tRNA 结构。尽管缺少所有接头残基，mascRNA 仍忠实地再现了 tRNA 的“肘部”特征，以招募 RNase P 和ElaC同源蛋白 2 (ELAC2) 进行加工，表现出独特的底物特异性。 D 茎和反密码子区域的旋转和重新定位可防止 mascRNA 氨酰化，从而避免干扰翻译。因此，一类后生动物 lncRNA 位点使用以前未被识别的、异常精简的准 tRNA 结构来招募选定的 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。