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Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs

Dhir, Ashish; Dhir, Somdutta; Proudfoot, Nick J.; Jopling, Catherine L.

Authors

Ashish Dhir ashish.dhir@path.ox.ac.uk

Somdutta Dhir somdutta.dhir@path.ox.ac.uk

Nick J. Proudfoot nicholas.proudfoot@path.ox.ac.uk



Abstract

MicroRNA (miRNA) play a major role in the post-transcriptional regulation of gene expression. Mammalian miRNA biogenesis begins with co-transcriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex. While most miRNA are located within introns of protein coding genes, a substantial minority of miRNA originate from long non coding (lnc) RNA where transcript processing is largely uncharacterized. Here, by detailed characterization of liver-specific lnc-pri-miR-122 and genome-wide analysis, we show that most lnc-pri-miRNA do not use the canonical cleavage and polyadenylation (CPA) pathway but instead use Microprocessor cleavage to terminate transcription. Microprocessor inactivation leads to extensive transcriptional readthrough of lnc-pri-miRNA and transcriptional interference with downstream genes. Consequently we define a novel RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells.

Journal Article Type Article
Publication Date Mar 2, 2015
Journal Nature Structural and Molecular Biology
Print ISSN 1545-9993
Electronic ISSN 1545-9993
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 22
APA6 Citation Dhir, A., Dhir, S., Proudfoot, N. J., & Jopling, C. L. (2015). Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs. Nature Structural and Molecular Biology, 22, doi:10.1038/nsmb.2982
DOI https://doi.org/10.1038/nsmb.2982
Keywords miRNA, lncRNA, transcription termination, gene expression
Publisher URL http://www.nature.com/nsmb/journal/v22/n4/full/nsmb.2982.html
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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