4rcm
Crystal structure of the Pho92 YTH domain in complex with m6A
Structural highlights
FunctionMRB1_YEAST RNA-binding protein that acts as a post-transcriptional regulator of phosphate metabolism by binding to the 3'-UTR region of PHO4 mRNA, decreasing its stability. Acts by recognizing and binding N6-methyladenosine (m6A)-containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs.[1] [2] Publication Abstract from PubMedN6-methyladenosine (m6A) is the most abundant internal modification in RNA and is specifically recognized by YTH domain containing proteins. Recently we reported that YTHDC1 prefers guanosine and disfavors adenosine at the position preceding the m6A nucleotide in RNA and preferentially binds to the GG(m6A)C sequence. Now we systematically characterized the binding affinities of the YTH domains of three other human proteins and yeast YTH domain protein Pho92, and determined the crystal structures of the YTH domains of human YTHDF1 and yeast Pho92 in complex with a 5-mer m6A RNA, respectively. Our binding and structural data revealed that the YTH domain used a conserved aromatic cage to recognize m6A. Nevertheless, none of these YTH domains, except YTHDC1, display sequence selectivity at the position preceding the m6A modification. Structural comparison of these different YTH domains revealed that among those, only YTHDC1 harbours a distinctly selective binding pocket for the nucleotide preceding the m6A nucleotide. Structural basis for the discriminative recognition of N6-methyladenosine RNA by the human YT521-B homology domain family of proteins.,Xu C, Liu K, Ahmed H, Loppnau P, Schapira M, Min J J Biol Chem. 2015 Aug 28. pii: jbc.M115.680389. PMID:26318451[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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