Multiple and Specific mRNA Processing Targets for the Major Human hnRNP Proteins
- 1 October 2008
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 28 (19), 6033-6043
- https://doi.org/10.1128/mcb.00726-08
Abstract
Alternative splicing is a key mechanism regulating gene expression, and it is often used to produce antagonistic activities particularly in apoptotic genes. Heterogeneous nuclear ribonucleoparticle (hnRNP) proteins form a family of RNA-binding proteins that coat nascent pre-mRNAs. Many but not all major hnRNP proteins have been shown to participate in splicing control. The range and specificity of hnRNP protein action remain poorly documented, even for those affecting splice site selection. We used RNA interference and a reverse transcription-PCR screening platform to examine the implications of 14 of the major hnRNP proteins in the splicing of 56 alternative splicing events in apoptotic genes. Out of this total of 784 alternative splicing reactions tested in three human cell lines, 31 responded similarly to a knockdown in at least two different cell lines. On the other hand, the impact of other hnRNP knockdowns was cell line specific. The broadest effects were obtained with hnRNP K and C, two proteins whose role in alternative splicing had not previously been firmly established. Different hnRNP proteins affected distinct sets of targets with little overlap even between closely related hnRNP proteins. Overall, our study highlights the potential contribution of all of these major hnRNP proteins in alternative splicing control and shows that the targets for individual hnRNP proteins can vary in different cellular contexts.Keywords
This publication has 63 references indexed in Scilit:
- Diverse roles of hnRNP L in mammalian mRNA processing: A combined microarray and RNAi analysisRNA, 2007
- Protein Kinase C-Dependent Control of Bcl-x Alternative SplicingMolecular and Cellular Biology, 2007
- Osteopontin‐c is a selective marker of breast cancerInternational Journal of Cancer, 2007
- A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neuronsGenes & Development, 2007
- hnRNP I/PTB can antagonize the splicing repressor activity of SRp30cRNA, 2007
- The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-xThe Journal of cell biology, 2007
- Functional coordination of alternative splicing in the mammalian central nervous systemGenome Biology, 2007
- An RNA map predicting Nova-dependent splicing regulationNature, 2006
- Nova regulates brain-specific splicing to shape the synapseNature Genetics, 2005
- Understanding alternative splicing: towards a cellular codeNature Reviews Molecular Cell Biology, 2005