@article{424c185ec0d14185b60b9e32cd03ac67,
title = "RBM-5 modulates U2AF large subunit-dependent alternative splicing in C. elegans",
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.",
keywords = "3ʹ splice site, RBM5, RNA splicing, U2AF, transcriptome",
author = "Chuanman Zhou and Xiaoyang Gao and Surong Hu and Wenjing Gan and Jing Xu and Ma, {Yongchao C.} and Long Ma",
note = "Funding Information: This work was supported by the National Key R&D Program of China [2016YFC1201805], National Natural Science Foundation of China [31371253] and National Natural Science Foundation of China [31571045] to LM; National Institutes of Health grant numbers R01NS094564 and R21NS106307 to YCM. This study was initiated in the laboratory of H. Robert Horvitz (HRH). H.R.H. is the David H. Koch Professor of Biology at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. We thank members of the Ma laboratory for suggestions. The study is supported by National Natural Science Foundation of China grants (No. 31371253, No. 31571045) and a MOST grant (2016YFC1201805) to LM. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Funding Information: This study was initiated in the laboratory of H. Robert Horvitz (HRH). H.R. H. is the David H. Koch Professor of Biology at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. We thank members of the Ma laboratory for suggestions. The study is supported by National Natural Science Foundation of China grants (No. 31371253, No. 31571045) and a MOST grant (2016YFC1201805) to LM. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Funding Information: This work was supported by the National Key R&D Program of China [2016YFC1201805], National Natural Science Foundation of China [31371253] and National Natural Science Foundation of China [31571045] to LM; National Institutes of Health grant numbers R01NS094564 and R21NS106307 to YCM. Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",
year = "2018",
month = oct,
day = "3",
doi = "10.1080/15476286.2018.1526540",
language = "English (US)",
volume = "15",
pages = "1295--1308",
journal = "RNA Biology",
issn = "1547-6286",
publisher = "Landes Bioscience",
number = "10",
}