Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs

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

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.

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, https://doi.org/10.1038/nsmb.2982

• 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: 1545-9985
• 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