tRNA-Derived RNA Fragments Associate with Human Multisynthetase Complex (MSC) and Modulate Ribosomal Protein Translation

The functionality of small RNAs from abundant species of “housekeeping” noncoding RNAs (e.g., rRNA, tRNA, snRNA, snoRNA, etc.) remains a highly studied topic. The current state of research on short RNAs derived from transfer RNA (tRNA), called tRNA-derived fragments (tRFs), has been restricted largely to expression studies and limited functional studies. 5′ tRFs are known translational inhibitors in mammalian cells, yet little is known about their functionality. Here we report on the first experimental evidence of the tRF protein interactome, identifying the mammalian multisynthetase complex as the primary interactor of the 5′ tRF Gln19. We also present proteome-wide SILAC evidence that 5′ tRFs increase ribosomal and poly­(A)-binding protein translation.源自高丰度“管家”型非编码RNA（如核糖体RNA（rRNA）、转运RNA（tRNA）、小核RNA（snRNA）、小核仁RNA（snoRNA）等）的小RNA的功能，仍是当前广受研究的热点课题。目前针对转运RNA（tRNA）衍生的短RNA——即tRNA衍生片段（tRFs）——的研究，大多仅局限于表达分析与有限的功能探究。已知5'端tRNA衍生片段（5′ tRFs）在哺乳动物细胞中可作为翻译抑制剂，但其具体功能仍鲜为人知。本研究首次报道了tRF蛋白质相互作用组的实验证据，鉴定出哺乳动物多合成酶复合物为5'端tRNA衍生片段Gln19的主要相互作用靶点。此外，本研究还提供了全蛋白质组级稳定同位素标记氨基酸细胞培养（SILAC）实验证据，表明5'端tRNA衍生片段可促进核糖体蛋白与poly(A)结合蛋白的翻译过程。