Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs.
MicroRNAs (miRNAs) play a major part in the post-transcriptional regulation of gene expression. Mammalian miRNA biogenesis begins with cotranscriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex. Although most miRNAs are located within introns of protein-coding transcripts, a substantial minority of miRNAs originate from long noncoding (lnc) RNAs, for which transcript processing is largely uncharacterized. We show, by detailed characterization of liver-specific lnc-pri-miR-122 and genome-wide analysis in human cell lines, that most lncRNA transcripts containing miRNAs (lnc-pri-miRNAs) do not use the canonical cleavage-and-polyadenylation 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 new RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Ashish
A
Dhir
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Somdutta
S
Dhir
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Nick J
NJ
Proudfoot
School of Pharmacy, University of Nottingham, Nottingham, UK.
Catherine L
CL
Jopling
D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D008957:Models, Genetic; D012323:RNA Processing, Post-Transcriptional; D062085:RNA, Long Noncoding / Q000378:metabolism*; D014158:Transcription, Genetic
C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding