Evidence for Existence of Multiple Functional Human Small RNAs Derived from Transcripts of Protein-coding Genes I

Human genome encodes a multitude of different non-coding transcripts that have been traditionally separated based on their lengths into long or small non-coding RNAs. The vast majority of both long and short non-coding transcripts are not annotated and their functions, mechanisms of action and biological relevance remain unknown. However, based on the functional understanding of the known classes of long and small non-coding RNAs (sncRNAs) that have been shown to play crucial roles in multiple biological processes, it is generally assumed that many unannotated long and small transcripts participate in important cellular functions as well. Still, direct evidence of functionality is lacking for most non-coding transcripts, especially for sncRNAs that are often dismissed as stable degradation products of longer RNAs. Here, we have developed a high-throughput assay to test functionality of sncRNAs based on overexpressing them in human cells. Surprisingly, we found that a significant fraction (> 40%) unannotated sncRNAs appear to have biological relevance. Furthermore, contrary to the expectation, the potentially functional transcripts are not highly abundant and can be derived from protein-coding mRNAs. These results strongly suggest that the small non-coding transcriptome can harbor multiple functional transcripts that warrant future studies. Functional analysis of novel small non-coding (snc) RNAs found in human K562 cell line.

人类基因组编码大量多样的非编码转录本，传统上依据其长度将其划分为长链非编码RNA（long non-coding RNA）与小非编码RNA（small non-coding RNA, sncRNA）。绝大多数长链及小非编码转录本尚未得到注释，其功能、作用机制及生物学意义仍未明确。尽管已知的长链与小非编码RNA（sncRNA）类别已被证实可在多种生物学过程中发挥关键作用，基于对这类RNA的功能认知，学界普遍推测众多未注释的长链与小非编码转录本同样参与重要的细胞功能活动。但绝大多数非编码转录本，尤其是常被视作长链RNA稳定降解产物的小非编码RNA，仍缺乏功能直接证据。本研究开发了一种在人类细胞中过表达小非编码RNA以检测其功能的高通量实验方法。令人意外的是，我们发现超过40%的未注释小非编码RNA似乎具有生物学意义。此外，与学界预期相悖的是，这些具备潜在功能的转录本表达丰度并不高，且可源自编码蛋白质的信使RNA（messenger RNA, mRNA）。上述研究结果有力表明，小非编码转录组中可蕴含大量具备功能的转录本，值得后续开展深入研究。本数据集针对人类K562细胞系中发现的新型小非编码（snc）RNA开展功能分析。