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PMID:24375645

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Citation

Xu, E, Zhang, J, Zhang, M, Jiang, Y, Cho, SJ and Chen, X (2014) RNA-binding protein RBM24 regulates p63 expression via mRNA stability. Mol. Cancer Res. 12:359-69

Abstract

p63, a p53 family member, plays pivotal roles in epidermal development, aging, and tumorigenesis. Thus, understanding how p63 expression is controlled has biological and clinical importance. RBM24 is an RNA-binding protein and shares a high sequence similarity with RBM38, a critical regulator of p63. In this study, we investigated whether RBM24 is capable of regulating p63 expression. Indeed, we found that ectopic expression of RBM24 decreased, whereas knockdown of RBM24 increased, the levels of p63 transcript and protein. To explore the underlying mechanism, we found that RBM24 was able to bind to multiple regions in the p63 3' untranslated region and, subsequently, destabilize p63 transcript. Furthermore, we showed that the 3' untranslated region in p63 transcript and the RNA-binding domain in RBM24 were required for RBM24 to bind p63 transcript and consequently, inhibit p63 expression. Taken together, our data provide evidence that RBM24 is a novel regulator of p63 via mRNA stability.

Links

PubMed PMC3962715 Online version:10.1158/1541-7786.MCR-13-0526

Keywords

3' Untranslated Regions; Amino Acid Sequence; Animals; Cell Differentiation/physiology; Gene Expression; Gene Knockdown Techniques; HCT116 Cells; Humans; MCF-7 Cells; Mice; Molecular Sequence Data; Plasmids/genetics; RNA Stability; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Transcription Factors/biosynthesis; Transcription Factors/genetics; Tumor Suppressor Proteins/biosynthesis; Tumor Suppressor Proteins/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:RBM24

GO:0061158: 3'-UTR-mediated mRNA destabilization

ECO:0000314:

P

Organism: Homo sapiens. Protein Name: RNA-Binding Protein RBM24. Notes: Figures 5G-H and 6D-E are used. First, the former two figures prove that RBM24 destabilizes the mRNA of p63. The paper states that “the half-life of ΔNp63 mRNA was deceased from 3.7 hours in the control cells to 2.7 hours in cells with RBM24 expression, and the half-life of TAp63 mRNA was deceased from 9.3 hours in the control cells to 7.2 hours in cells with RBM24 expression.” As can be seen in the line graphs, the p63 transcripts destabilize more quickly in the presence of RBM24. Thus, RBM24 is linked to mRNA destabilization. It is also linked to 3’UTR-mediated mRNA destabilization in particular, as proven by Figures 6D-E. As the paper states, “we found that RBM24 had no effect on TAp63α expression from an expression vector that only contains TAp63α coding sequence (Fig. 6D). By contrast, TAp63α expression was significantly inhibited by RBM24 when the TAp63α expression vector contains a full-length p63 3′UTR (Fig. 6E).” In Figure 6D, it can be seen that the relative level of TAp63α barely changed when RBM24 was transfected into the cells. However, in Figure 6E, the level decreased significantly, due to the presence of a 3’UTR region. Thus, the inhibition of p63 occurs by the destabilization of its transcripts, specifically the 3’UTR region of mRNA. This links RBM24 to 3’UTR-mediated mRNA destabilization.

complete
CACAO 12379

HUMAN:RBM24

enables

GO:0003730: mRNA 3'-UTR binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:RBM24

involved_in

GO:0061158: 3'-UTR-mediated mRNA destabilization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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