Meta-Biol

• Pathways

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.

RNA elements rich in adenine and uracil residues (AU-rich elements) bind specific proteins which either target the RNA for degradation or, more rarely, stabilize the RNA. The activity of the AU-element binding proteins is regulated, usually by phosphorylation but also by subcellular localization.

This superpathway encompasses the processes by which RNA transcription products are further modified covalently and non-covalently to yield their mature forms, and the regulation of these processes. Annotated pathways include ones for capping, splicing, and 3'-cleavage and polyadenylation to yield mature mRNA molecules that are exported from the nucleus (Hocine et al. 2010). mRNA editing and nonsense-mediated decay are also annotated. Processes leading to mRNA breakdown are described: deadenylation-dependent mRNA decay, microRNA-mediated RNA cleavage, and regulation of mRNA stability by proteins that bind AU-rich elements.psnRNP assembly is also annotated here.

The aminoacylation of mature tRNAs is annotated in the "Metabolism of proteins" superpathway, as a part of "Translation".