Feed-forward microprocessing and splicing activities at a microRNA-containing intron.

The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed fro...

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Main Authors: Maja M Janas, Mehdi Khaled, Steffen Schubert, Jacob G Bernstein, David Golan, Rosa A Veguilla, David E Fisher, Noam Shomron, Carmit Levy, Carl D Novina
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-10-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC3197686?pdf=render
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author Maja M Janas
Mehdi Khaled
Steffen Schubert
Jacob G Bernstein
David Golan
Rosa A Veguilla
David E Fisher
Noam Shomron
Carmit Levy
Carl D Novina
author_facet Maja M Janas
Mehdi Khaled
Steffen Schubert
Jacob G Bernstein
David Golan
Rosa A Veguilla
David E Fisher
Noam Shomron
Carmit Levy
Carl D Novina
author_sort Maja M Janas
collection DOAJ
description The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6-exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5' splice site (5'SS), but not in the 3'SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5'SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs.
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spelling doaj.art-4f3eba0b377444649e173cfb613834ef2022-12-21T18:45:39ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-10-01710e100233010.1371/journal.pgen.1002330Feed-forward microprocessing and splicing activities at a microRNA-containing intron.Maja M JanasMehdi KhaledSteffen SchubertJacob G BernsteinDavid GolanRosa A VeguillaDavid E FisherNoam ShomronCarmit LevyCarl D NovinaThe majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6-exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5' splice site (5'SS), but not in the 3'SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5'SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs.http://europepmc.org/articles/PMC3197686?pdf=render
spellingShingle Maja M Janas
Mehdi Khaled
Steffen Schubert
Jacob G Bernstein
David Golan
Rosa A Veguilla
David E Fisher
Noam Shomron
Carmit Levy
Carl D Novina
Feed-forward microprocessing and splicing activities at a microRNA-containing intron.
PLoS Genetics
title Feed-forward microprocessing and splicing activities at a microRNA-containing intron.
title_full Feed-forward microprocessing and splicing activities at a microRNA-containing intron.
title_fullStr Feed-forward microprocessing and splicing activities at a microRNA-containing intron.
title_full_unstemmed Feed-forward microprocessing and splicing activities at a microRNA-containing intron.
title_short Feed-forward microprocessing and splicing activities at a microRNA-containing intron.
title_sort feed forward microprocessing and splicing activities at a microrna containing intron
url http://europepmc.org/articles/PMC3197686?pdf=render
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