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Identification of alternative splicing regulators by RNA interference in Drosophila.


ABSTRACT: Alternative splicing is thought to be regulated by nonspliceosomal RNA binding proteins that modulate the association of core components of the spliceosome with the pre-mRNA. Although the majority of metazoan genes encode pre-mRNAs that are alternatively spliced, remarkably few splicing regulators are currently known. Here, we used RNA interference to examine the role of >70% of the Drosophila RNA-binding proteins in regulating alternative splicing. We identified 47 proteins as splicing regulators, 26 of which have not previously been implicated in alternative splicing. Many of the regulators we identified are nonspliceosomal RNA-binding proteins. However, our screen unexpectedly revealed that altering the concentration of certain core components of the spliceosome specifically modulates alternative splicing. These results significantly expand the number of known splicing regulators and reveal an extraordinary richness in the mechanisms that regulate alternative splicing.

SUBMITTER: Park JW 

PROVIDER: S-EPMC528766 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature

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Identification of alternative splicing regulators by RNA interference in Drosophila.

Park Jung W JW   Parisky Katherine K   Celotto Alicia M AM   Reenan Robert A RA   Graveley Brenton R BR  

Proceedings of the National Academy of Sciences of the United States of America 20041018 45


Alternative splicing is thought to be regulated by nonspliceosomal RNA binding proteins that modulate the association of core components of the spliceosome with the pre-mRNA. Although the majority of metazoan genes encode pre-mRNAs that are alternatively spliced, remarkably few splicing regulators are currently known. Here, we used RNA interference to examine the role of >70% of the Drosophila RNA-binding proteins in regulating alternative splicing. We identified 47 proteins as splicing regulato  ...[more]

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