Distinctive Patterns of Transcription and RNA Processing for Human LincRNAs

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Dec 27

PMID 28017589

Citations 149

Authors

Margarita Schlackow

Takayuki Nojima

Tomas Gomes

Ashish Dhir

Maria Carmo-Fonseca

Nick J Proudfoot

Affiliations

Soon will be listed here.

Abstract

Numerous long intervening noncoding RNAs (lincRNAs) are generated from the mammalian genome by RNA polymerase II (Pol II) transcription. Although multiple functions have been ascribed to lincRNAs, their synthesis and turnover remain poorly characterized. Here, we define systematic differences in transcription and RNA processing between protein-coding and lincRNA genes in human HeLa cells. This is based on a range of nascent transcriptomic approaches applied to different nuclear fractions, including mammalian native elongating transcript sequencing (mNET-seq). Notably, mNET-seq patterns specific for different Pol II CTD phosphorylation states reveal weak co-transcriptional splicing and poly(A) signal-independent Pol II termination of lincRNAs as compared to pre-mRNAs. In addition, lincRNAs are mostly restricted to chromatin, since they are rapidly degraded by the RNA exosome. We also show that a lincRNA-specific co-transcriptional RNA cleavage mechanism acts to induce premature termination. In effect, functional lincRNAs must escape from this targeted nuclear surveillance process.

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