RBM5 promotes exon 4 skipping of <i>AID</i> pre‐mRNA by competing with the binding of U2AF65 to the polypyrimidine tract

Jin, Wei; Niu, Zhaoyang; Xu, Dan; Li, Xialu

doi:10.1016/j.febslet.2012.09.006

Cited by 23 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RBM5 was frequently deleted or mutated in lung cancers [19] and can affect alternative splicing, cell proliferation and apoptosis [19,30,32,40]. In C. elegans , the function of rbm-5 is unclear.…”

Section: Resultsmentioning

confidence: 99%

“…Mammalian RBM5 can affect the splicing of different genes [30–32,40]. We examined whether rbm-5 mutations can affect RNA splicing in C. elegans and how rbm-5 interacts with uaf-1 in doing so.…”

Section: Resultsmentioning

confidence: 99%

“…In mammals, RBM5 can affect splicing especially at weak 3ʹ SS [30,32,40], which might depend on RBM5 binding to multiple different cis RNA sequences [31,32,40,55]. RBM5 was isolated as an interacting protein of U2AF large subunit and their interaction requires the RS domain of U2AF large subunit and the C-terminal region of RBM5 [30].…”

Section: Discussionmentioning

confidence: 99%

“…In mammals, RBM5 can physically bind U2AF large subunit [30] and may also compete with U2AF large subunit for binding to the polypyrimidine tract [32]. RBM5 also binds multiple different cis RNA sequences [31,32,40,55].…”

Section: Discussionmentioning

confidence: 99%

“…RBM5 also binds multiple different cis RNA sequences [31,32,40,55]. Recent genome-wide studies suggest that several RNA-binding proteins affect splicing by modulating the binding of U2AF large subunit to alternative 3ʹ SS [59,60].…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

RBM-5 modulates U2AF large subunit-dependent alternative splicing inC. elegans

Zhou

Gao

et al. 2018

RNA Biology

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

RBM-5 modulates U2AF large subunit-dependent alternative splicing inC. elegans

Zhou

Gao

et al. 2018

RNA Biology

View full text Add to dashboard Cite

show abstract

Post-transcriptional regulation of Rbm5 expression in undifferentiated H9c2 myoblasts

Loiselle

Tessier

Sutherland

2015

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

We previously examined the expression of Rbm5 during myoblast differentiation and found significantly more protein in the early stages of skeletal myoblast differentiation than during the later stages. We decided to determine if this elevated level was necessary for differentiation. Our hypothesis was that if high levels of Rbm5 protein expression were necessary for the initiation of skeletal myoblast differentiation, then inhibition of expression would prevent differentiation. Our long-term objective is to inhibit Rbm5 expression and examine the effect on H9c2 differentiation. Towards this end, stable knockdown clones and transient knockdown populations were generated. Expression analyses in H9c2 myoblasts demonstrated significant Rbm5 messenger RNA (mRNA) inhibition but, surprisingly, no effect on RBM5 protein levels. Expression of the Rbm5 paralogue Rbm10 was examined in order to (a) ensure no off-target knockdown effect, and (b) investigate any possible compensatory effects. RBM10 protein levels were found to be elevated, in both the clonal and transiently transfected populations. These results suggest that myoblast RBM5 expression is regulated by a process that includes RNA sequestration and/or controlled translation, and that (a) RBM5 function is compensated for by RBM10, and/or (b) RBM5 regulates RBM10 expression. We have developed a model to describe our findings, and suggest further experiments for testing its validity. Since upregulation of Rbm10 might compensate for downregulated Rbm5, and consequently might mask any potential knockdown effect, it could lead to incorrect conclusions regarding the importance of Rbm5 for differentiation. It is therefore imperative to determine how both RBM5 and RBM10 protein expression is regulated.

show abstract