Abstract
A key step in pre-mRNA splicing is the recognition of 3ʹ splicing sites by the U2AF large and small subunits, a process regulated by numerous trans-acting splicing factors. How these trans-acting factors interact with U2AF in vivo is unclear. From a screen for suppressors of the temperature-sensitive (ts) lethality of the C. elegans U2AF large subunit gene uaf-1(n4588) mutants, we identified mutations in the RNA binding motif gene rbm-5, a homolog of the tumor suppressor gene RBM5. rbm-5 mutations can suppress uaf-1(n4588) ts-lethality by loss of function and neuronal expression of rbm-5 was sufficient to rescue the suppression. Transcriptome analyses indicate that uaf-1(n4588) affected the expression of numerous genes and rbm-5 mutations can partially reverse the abnormal gene expression to levels similar to that of wild type. Though rbm-5 mutations did not obviously affect alternative splicing per se, they can suppress or enhance, in a gene-specific manner, the altered splicing of genes in uaf-1(n4588) mutants. Specifically, the recognition of a weak 3ʹ splice site was more susceptible to the effect of rbm-5. Our findings provide novel in vivo evidence that RBM-5 can modulate UAF-1-dependent RNA splicing and suggest that RBM5 might interact with U2AF large subunit to affect tumor formation.
Original language | English (US) |
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Pages (from-to) | 1295-1308 |
Number of pages | 14 |
Journal | RNA biology |
Volume | 15 |
Issue number | 10 |
DOIs | |
State | Published - Oct 3 2018 |
Keywords
- 3ʹ splice site
- RBM5
- RNA splicing
- U2AF
- transcriptome
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
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RBM-5 modulates U2AF large subunit-dependent alternative splicing in C. elegans
Zhou, C. (Contributor), Gao, X. (Contributor), Hu, S. (Contributor), Gan, W. (Contributor), Xu, J. (Creator), Ma, Y. C. (Creator) & Ma, L. (Creator), Taylor & Francis, 2018
DOI: 10.6084/m9.figshare.7177790.v2, https://tandf.figshare.com/articles/RBM-5_modulates_U2AF_large_subunit-dependent_alternative_splicing_in_i_C_elegans_i_/7177790/2
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