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The first step in microRNA (miRNA) biogenesis occurs in the nucleus and is mediated by the Microprocessor complex containing the RNase III-like enzyme Drosha and its cofactor DGCR8. Here we show that the 5'-->3' exonuclease Xrn2 associates with independently transcribed miRNAs and, in combination with Drosha processing, attenuates transcription in downstream regions. We suggest that, after Drosha cleavage, a torpedo-like mechanism acts on nascent long precursor miRNAs, whereby Xrn2 exonuclease degrades the RNA polymerase II-associated transcripts inducing its release from the template. While involved in primary transcript termination, this attenuation effect does not restrict clustered miRNA expression, which, in the majority of cases, is separated by short spacers. We also show that transcripts originating from a miRNA promoter are retained on the chromatin template and are more efficiently processed than those produced from mRNA or snRNA Pol II-dependent promoters. These data imply that coupling between transcription and processing promotes efficient expression of independently transcribed miRNAs.

Original publication

DOI

10.1128/MCB.00664-09

Type

Journal article

Journal

Mol Cell Biol

Publication Date

10/2009

Volume

29

Pages

5632 - 5638

Keywords

Cell Line, Tumor, Exoribonucleases, HeLa Cells, Humans, MicroRNAs, Promoter Regions, Genetic, Proteins, RNA Polymerase II, RNA Processing, Post-Transcriptional, RNA, Messenger, RNA, Small Nuclear, RNA-Binding Proteins, Ribonuclease III