Structural highlights
Function
[CIRBP_HUMAN] Cold-inducible mRNA binding protein that plays a protective role in the genotoxic stress response by stabilizing transcripts of genes involved in cell survival. Acts as a translational activator. Seems to play an essential role in cold-induced suppression of cell proliferation. Binds specifically to the 3'-untranslated regions (3'-UTRs) of stress-responsive transcripts RPA2 and TXN. Acts as a translational repressor (By similarity). Promotes assembly of stress granules (SGs), when overexpressed.[1] [2]
Publication Abstract from PubMed
The heterogeneous ribonucleoprotein A18 (hnRNP A18) is upregulated in hypoxic regions of various solid tumors and promotes tumor growth via the coordination of mRNA transcripts associated with pro-survival genes. Thus, hnRNP A18 represents an important therapeutic target in tumor cells. Presented here is the first X-ray crystal structure to be reported for the RNA-recognition motif of hnRNP A18. By comparing this structure with those of homologous RNA-binding proteins (i.e. hnRNP A1), three residues on one face of an antiparallel beta-sheet (Arg48, Phe50 and Phe52) and one residue in an unstructured loop (Arg41) were identified as likely to be involved in protein-nucleic acid interactions. This structure helps to serve as a foundation for biophysical studies of this RNA-binding protein and structure-based drug-design efforts for targeting hnRNP A18 in cancer, such as malignant melanoma, where hnRNP A18 levels are elevated and contribute to disease progression.
Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif.,Coburn K, Melville Z, Aligholizadeh E, Roth BM, Varney KM, Carrier F, Pozharski E, Weber DJ Acta Crystallogr F Struct Biol Commun. 2017 Apr 1;73(Pt 4):209-214. doi:, 10.1107/S2053230X17003454. Epub 2017 Mar 22. PMID:28368279[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yang C, Carrier F. The UV-inducible RNA-binding protein A18 (A18 hnRNP) plays a protective role in the genotoxic stress response. J Biol Chem. 2001 Dec 14;276(50):47277-84. Epub 2001 Sep 26. PMID:11574538 doi:http://dx.doi.org/10.1074/jbc.M105396200
- ↑ Yang R, Weber DJ, Carrier F. Post-transcriptional regulation of thioredoxin by the stress inducible heterogenous ribonucleoprotein A18. Nucleic Acids Res. 2006 Mar 2;34(4):1224-36. Print 2006. PMID:16513844 doi:http://dx.doi.org/10.1093/nar/gkj519
- ↑ Coburn K, Melville Z, Aligholizadeh E, Roth BM, Varney KM, Carrier F, Pozharski E, Weber DJ. Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif. Acta Crystallogr F Struct Biol Commun. 2017 Apr 1;73(Pt 4):209-214. doi:, 10.1107/S2053230X17003454. Epub 2017 Mar 22. PMID:28368279 doi:http://dx.doi.org/10.1107/S2053230X17003454
