Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs
Dhir, Ashish and Dhir, Somdutta and Proudfoot, Nick J. and Jopling, Catherine L. (2015) Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs. Nature Structural and Molecular Biology, 22 . pp. 319-327. ISSN 1545-9993
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.
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