Institute of Genomics, School of Medicine, Huaqiao University, 668 Jimei Road, Xiamen 361021, China.
Int J Mol Sci. 2023 Feb 19;24(4):4163. doi: 10.3390/ijms24044163.
The human genome encodes a multitude of different noncoding transcripts that have been traditionally separated on the basis of their lengths into long (>200 nt) or small (<200 nt) noncoding RNAs. The functions, mechanisms of action, and biological relevance of the vast majority of both long and short noncoding transcripts remain unknown. However, according to the functional understanding of the known classes of long and small noncoding 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. Nevertheless, direct evidence of functionality is lacking for most noncoding transcripts, especially for sncRNAs that are often dismissed as stable degradation products of longer RNAs. Here, we developed a high-throughput assay to test the functionality of sncRNAs by overexpressing them in human cells. Surprisingly, we found that a significant fraction (>40%) of 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 noncoding transcriptome can harbor multiple functional transcripts that warrant future studies.
人类基因组编码了大量不同的非编码转录本，这些转录本传统上根据其长度分为长 (>200nt) 或小 (<200nt) 非编码 RNA。绝大多数长链和短链非编码 RNA 的功能、作用机制和生物学相关性仍然未知。然而，根据已知长链和短链非编码 RNA (sncRNA) 类别的功能理解，这些 RNA 已被证明在多种生物过程中发挥关键作用，人们普遍认为许多未注释的长链和短链转录本也参与重要的细胞功能。然而，大多数非编码转录本缺乏直接的功能证据，尤其是那些经常被认为是更长 RNA 稳定降解产物的 sncRNA。在这里，我们开发了一种高通量测定法，通过在人细胞中转录本过表达来测试 sncRNA 的功能。令人惊讶的是，我们发现很大一部分 (>40%) 的未注释 sncRNA 似乎具有生物学相关性。此外，与预期相反，潜在功能转录本的丰度并不高，并且可以来自编码蛋白质的 mRNA。这些结果强烈表明，小非编码转录组可能包含多个需要进一步研究的功能转录本。
