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...
Main Authors: | , , , , , , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2011-10-01
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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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institution | Directory Open Access Journal |
issn | 1553-7390 1553-7404 |
language | English |
last_indexed | 2024-12-22T00:02:07Z |
publishDate | 2011-10-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS Genetics |
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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