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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.

Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs Thumbnail


Authors

Ashish Dhir

Somdutta Dhir

Nick J. Proudfoot



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
Deposit Date Jul 1, 2015
Publicly Available Date Jul 1, 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
DOI https://doi.org/10.1038/nsmb.2982
Keywords miRNA, lncRNA, transcription termination, gene expression
Public URL https://nottingham-repository.worktribe.com/output/748269
Publisher URL http://www.nature.com/nsmb/journal/v22/n4/full/nsmb.2982.html

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