RNA. 2014 Feb;20(2):236-51. doi: 10.1261/rna.038927.113. Epub 2013 Dec 16.
The past decade has shown mammalian genomes to be pervasively transcribed and identified thousands of noncoding (nc) transcripts. It is currently unclear to what extent these transcripts are of functional importance, as experimental functional evidence exists for only a small fraction. Here, we characterize the expression and evolutionary conservation properties of 12,115 known and novel nc transcripts, including structural RNAs, long nc RNAs (lncRNAs), antisense RNAs, EvoFold predictions, ultraconserved elements, and expressed nc regions. Expression levels are evaluated across 12 human tissues using a custom-designed microarray, supplemented with RNAseq. Conservation levels are evaluated at both the base level and at the syntenic level. We combine these measures with epigenetic mark annotations to identify subsets of novel nc transcripts that show characteristics similar to known functional ncRNAs. Few novel nc transcripts show both high expression and conservation levels. However, overall, we observe a positive correlation between expression and both conservation and epigenetic annotations, suggesting that a subset of the expressed transcripts are under purifying selection and likely functional. The identified subsets of expressed and conserved novel nc transcripts may form the basis for further functional characterization.
在过去的十年中,人们已经发现哺乳动物的基因组广泛转录,并鉴定出了数千种非编码(nc)转录本。目前还不清楚这些转录本在功能上有多么重要,因为只有一小部分转录本具有实验功能证据。在这里,我们描述了 12115 个已知和新的 nc 转录本的表达和进化保守特性,包括结构 RNA、长 ncRNA(lncRNA)、反义 RNA、EvoFold 预测、超保守元件和表达 nc 区域。使用定制的微阵列和 RNAseq 评估了这些转录本在 12 个人体组织中的表达水平。我们还在碱基水平和同线性水平评估了保守水平。我们将这些指标与表观遗传标记注释相结合,以确定具有与已知功能性 ncRNA 相似特征的新型 nc 转录本子集。很少有新型 nc 转录本同时具有高表达和保守水平。然而,总的来说,我们观察到表达水平与保守水平和表观遗传注释之间存在正相关关系,这表明一部分表达的转录本受到了纯化选择的影响,可能具有功能。所鉴定的表达和保守的新型 nc 转录本子集可能为进一步的功能特征提供基础。