Reactome | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA

Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA

Stable Identifier

R-HSA-450385

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA

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Butyrate Response Factor 1 (BRF1, ZFP36L1, not to be confused with transcription factor IIIB) binds AU-rich elements in the 3' region of mRNAs. After binding, BRF1 recruits exonucleases (XRN1 and the exosome) and decapping enzymes (DCP1a and DCP2) to hydrolyze the RNA. The ability of BRF1 to direct RNA degradation is controlled by phosphorylation of BRF1. Protein kinase B/AKT1 phosphorylates BRF1 at serines 92 and 203. Phosphorylated BRF1 can still bind RNA but is sequestered by binding 14-3-3 protein, preventing BRF1 from destabilizing RNA. BRF1 is also phosphorylated by MK2 at serines 54, 92, 203, and at an unknown site in the C-terminus. It is unknown if this particular phosphorylated form of BRF1 binds 14-3-3.

Literature References

PubMed ID	Title	Journal	Year
11719186	AU binding proteins recruit the exosome to degrade ARE-containing mRNAs Karin, M, Stoecklin, G, Ong, SE, Gherzi, R, Mann, M, Chan, EL, Chen, CY, Raijmakers, R, Moroni, C, Pruijn, GJ	Cell	2001
16391004	AU-rich elements and associated factors: are there unifying principles? Barreau, C, Paillard, L, Osborne, HB	Nucleic Acids Res	2005
15687258	Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1 Lykke-Andersen, J, Wagner, E	Genes Dev	2005
12704645	Post-transcriptional regulation of gene expression by degradation of messenger RNAs Ceriani, MC, Bevilacqua, A, Capaccioli, S, Nicolin, A	J Cell Physiol	2003
12440953	AU-rich element-mediated translational control: complexity and multiple activities of trans-activating factors Kruys, V, Zhang, T, Huez, G, Gueydan, C	Biochem Soc Trans	2002