RNA demethylase ALKBH5

Definition:

Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro). Requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA processing and export. Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells (By similarity).

References:

[1]. Guanqun Zheng, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013 Jan 10;49(1):18-29. [Content Brief]

[2]. Chong Feng, et al. Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition. J Biol Chem. 2014 Apr 25;289(17):11571-11583. [Content Brief]

[3]. Armin Thalhammer, et al. Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1α (HIF-1α). PLoS One. 2011 Jan 14;6(1):e16210. [Content Brief]

[4]. Chao Xu, et al. Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation. J Biol Chem. 2014 Jun 20;289(25):17299-311. [Content Brief]

[5]. WeiShen Aik, et al. Structure of human RNA N⁶-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation. Nucleic Acids Res. 2014 Apr;42(7):4741-54. [Content Brief]

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