Coupled RNA Processing and Transcription of Intergenic Primary MicroRNAs

Author:

Ballarino Monica1,Pagano Francesca1,Girardi Erika1,Morlando Mariangela12,Cacchiarelli Davide1,Marchioni Marcella1,Proudfoot Nicholas J.2,Bozzoni Irene1

Affiliation:

1. Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology and IBPM, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy

2. Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford OX1 3RE, United Kingdom

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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