Distinctive Patterns of Transcription and RNA Processing for Human lincRNAs

Margarita Schlackow, Takayuki Nojima, Tomas Gomes, Ashish Dhir, Maria Carmo-Fonseca, Nick J Proudfoot

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)25-38
Number of pages14
JournalMolecular Cell
Volume65
Issue number1
Early online date22 Dec 2016
DOIs
Publication statusPublished - 5 Jan 2017

Keywords / Materials (for Non-textual outputs)

  • Cell Nucleus/metabolism
  • Computational Biology
  • Databases, Genetic
  • Exosome Multienzyme Ribonuclease Complex/genetics
  • HeLa Cells
  • Humans
  • Phosphorylation
  • Polyadenylation
  • RNA Interference
  • RNA Polymerase II/metabolism
  • RNA Precursors/genetics
  • RNA Processing, Post-Transcriptional
  • RNA Splicing
  • RNA Stability
  • RNA, Long Noncoding/genetics
  • RNA, Messenger/genetics
  • Transcription, Genetic
  • Transfection

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