RNA stability defines the identity of long noncoding RNA in mammals

There is growing recognition that mammalian genomes produce huge number of long noncoding RNAs (ncRNAs). However, the biological functions of most long ncRNAs are still unclear. Here we report a new approach to uncover the discriminative property of the functional long ncRNAs by combination of comprehensively measuring the half-lives and functional analysis. Our approach reveals hundreds of short-lived ncRNAs in which many well-known functional long ncRNAs are sorted. Moreover, we provide strong evidence that modulation of half-lives of relatively short-lived functional long ncRNAs, viz. NEAT1/MEN ? and GAS5, alters functional consequence, and identified novel short-lived intergenic noncoding transcripts (SLITs), those degradations are regulated by stimuli, involving in cell proliferation. Together, these results propose that short-lived property of ncRNA will be key parameter for identifying the uncharacterized long ncRNAs.

越来越多的研究共识表明，哺乳动物基因组可产生海量长链非编码RNA（long noncoding RNAs, ncRNAs）。然而，绝大多数长链非编码RNA的生物学功能仍未明确。本研究报道了一种新方法，通过综合测定RNA半衰期与功能分析相结合的手段，揭示功能性长链非编码RNA的鉴别特征。我们的方法鉴定出数百种短半衰期非编码RNA，其中富集了诸多经典的功能性长链非编码RNA。此外，本研究提供了强有力的证据：调控相对短半衰期的功能性长链非编码RNA（如NEAT1/MEN ? 与GAS5）的半衰期，可改变其功能结局；同时鉴定出新型短半衰期基因间非编码转录本（short-lived intergenic noncoding transcripts, SLITs），其降解过程受外界刺激调控，并参与细胞增殖过程。综上，本研究结果提示，RNA的短半衰期特性将成为鉴定未表征长链非编码RNA的关键参数。