Dissecting the targeting rules of 5' tRNA halves

Fragments of mature tRNAs have long been considered as mere degradation products without physiological function. However, recent reports show that tRNA-derived small RNAs (tsRNAs) play prominent roles in diverse cellular processes across a wide spectrum of species. As it is the case for other classes of small RNAs, tsRNAs were found to affect gene expression in different contexts, but the mechanisms behind these effects appear more diverse, more complex and are generally less well understood. Here, we modulated the regulation capacity of selected 5' tRNA halves (tRH) in human cells by transfecting synthetic tRH mimics (“overexpression”) or antisense-RNAs (“inhibition”) and identified differentially expressed transcripts based on RNAseq. We then used a novel k-mer mapping approach to dissect the underlying targeting rules.

成熟转运RNA（transfer RNA, tRNA）的片段长期以来被认为仅是无生理功能的降解产物。然而，近期研究证实，tRNA衍生小RNA（tRNA-derived small RNAs, tsRNAs）在跨物种类群的多样细胞进程中发挥着关键作用。与其他类别的小RNA类似，tsRNAs已被发现可在不同情境下调控基因表达，但其介导此类调控效应的机制更为多样复杂，且总体而言尚未得到充分阐明。本研究通过向人类细胞中转染合成的tRH模拟物（“过表达”组）或反义RNA（“抑制”组），对所筛选的5'端tRNA半分子（5' tRNA halves, tRH）的调控能力进行干预，并基于RNA测序（RNAseq）鉴定差异表达转录本。随后，我们采用一种新型k聚体（k-mer）比对分析方法，解析其潜在的靶向作用规则。