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


ABSTRACT: 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.

SUBMITTER: Janas MM 

PROVIDER: S-EPMC3197686 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Janas Maja M MM   Khaled Mehdi M   Schubert Steffen S   Bernstein Jacob G JG   Golan David D   Veguilla Rosa A RA   Fisher David E DE   Shomron Noam N   Levy Carmit C   Novina Carl D CD  

PLoS genetics 20111020 10


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,  ...[more]

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