Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 290, Issue 41, Pages 24902-24913Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.680389
Keywords
-
Categories
Funding
- AbbVie
- Bayer Pharma AG
- Baehringer Ingelheim
- Canada Foundation for Innovation
- Eshelman Institute for Innovation
- Genome Canada
- Innovative Medicines Initiative (the European Federation of Pharmaceutical Industries and Associations (European Union)) under ULTRA-DD Grant [115766]
- Janssen
- Merck Co.
- Novartis Pharma AG
- Ontario Ministry of Economic Development and Innovation
- Pfizer
- Sao Paulo Research Foundation-Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Takeda
- Wellcome Trust
Ask authors/readers for more resources
N-6-Methyladenosine (m(6)A) is the most abundant internal modification in RNA and is specifically recognized by YT521-B homology (YTH) domain-containing proteins. Recently we reported that YTHDC1 prefers guanosine and disfavors adenosine at the position preceding the m(6)A nucleotide in RNA and preferentially binds to the GG(m(6)A)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 theYTH domains of human YTHDF1 and yeast Pho92 in complex with a 5-mer m(6)A RNA, respectively. Our binding and structural data revealed that the YTH domain used a conserved aromatic cage to recognize m(6)A. Nevertheless, none of these YTH domains, except YTHDC1, display sequence selectivity at the position preceding the m(6)A modification. Structural comparison of these different YTH domains revealed that among those, only YTHDC1 harbors a distinctly selective binding pocket for the nucleotide preceding the m(6)A nucleotide.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available