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Global regulation of alternative RNA splicing by the SR-rich protein RBM39.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2016 Aug; Vol. 1859 (8), pp. 1014-24. Date of Electronic Publication: 2016 Jun 21. - Publication Year :
- 2016
-
Abstract
- Background: RBM39 is a serine/arginine-rich RNA-binding protein that is highly homologous to the splicing factor U2AF65. However, the role of RBM39 in alternative splicing is poorly understood.<br />Methods: In this study, RBM39-mediated global alternative splicing was investigated using RNA-Seq and genome-wide RBM39-RNA interactions were mapped via cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq) in wild-type and RBM39-knockdown MCF-7 cells.<br />Results: RBM39 was involved in the up- or down-regulation of the transcript levels of various genes. Hundreds of alternative splicing events regulated by endogenous RBM39 were identified. The majority of these events were cassette exons. Genes containing RBM39-regulated alternative exons were found to be linked to G2/M transition, cellular response to DNA damage, adherens junctions and endocytosis. CLIP-Seq analysis showed that the binding site of RBM39 was mainly in proximity to 5' and 3' splicing sites. Considerable RBM39 binding to mRNAs encoding proteins involved in translation was observed. Of particular importance, ~20% of the alternative splicing events that were significantly regulated by RBM39 were similarly regulated by U2AF65.<br />Conclusions: RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65.<br />General Significance: The current study offers a genome-wide view of RBM39's regulatory function in alternative splicing. RBM39 may play important roles in multiple cellular processes by regulating both alternative splicing of RNA molecules and transcript levels.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Adherens Junctions genetics
Amino Acid Sequence
Arginine metabolism
Binding Sites
DNA Damage
Down-Regulation
Endocytosis genetics
G2 Phase Cell Cycle Checkpoints genetics
Gene Expression Profiling
HEK293 Cells
High-Throughput Nucleotide Sequencing
Humans
MCF-7 Cells
Nuclear Proteins metabolism
Protein Binding
RNA, Messenger metabolism
RNA-Binding Proteins metabolism
Sequence Homology, Amino Acid
Serine metabolism
Signal Transduction
Splicing Factor U2AF metabolism
Up-Regulation
Alternative Splicing
Nuclear Proteins genetics
RNA, Messenger genetics
RNA-Binding Proteins genetics
Splicing Factor U2AF genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1859
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 27354116
- Full Text :
- https://doi.org/10.1016/j.bbagrm.2016.06.007