title: Distinctive Patterns of Transcription and RNA Processing for Human lincRNAs.
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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Margarita
authors.initials: M
authors.lastname: Schlackow
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: taka.nojima@path.ox.ac.uk.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nojima
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Tomas
authors.initials: T
authors.lastname: Gomes
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Ashish
authors.initials: A
authors.lastname: Dhir
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Carmo-Fonseca
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: nicholas.proudfoot@path.ox.ac.uk.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Proudfoot
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D019295:Computational Biology; D030541:Databases, Genetic; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D026723:Polyadenylation; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D012322:RNA Precursors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012319:RNA Polymerase II; D063326:Exosome Multienzyme Ribonuclease Complex
keywords: CPSF73; empigen; exosome; lincRNA; mNET-seq; phosphor CTD marks; polyadenylation; splicing; transcription termination