m7GpppN-mRNA hydrolase

Definition:

Decapping metalloenzyme that catalyzes the cleavage of the cap structure on mRNAs. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Plays a role in replication-dependent histone mRNA degradation. Has higher activity towards mRNAs that lack a poly(A) tail. Has no activity towards a cap structure lacking an RNA moiety. The presence of a N(6)-methyladenosine methylation at the second transcribed position of mRNAs (N(6),2'-O-dimethyladenosine cap; m6A(m)) provides resistance to DCP2-mediated decapping. Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts.

References:

[1]. Man-Gen Song, et al. Multiple mRNA decapping enzymes in mammalian cells. Mol Cell. 2010 Nov 12;40(3):423-32. [Content Brief]

[2]. Jan Mauer, et al. Reversible methylation of m6Am in the 5' cap controls mRNA stability. Nature. 2017 Jan 19;541(7637):371-375. [Content Brief]

[3]. Zuoren Wang, et al. The hDcp2 protein is a mammalian mRNA decapping enzyme. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12663-8. [Content Brief]

[4]. Christopher Piccirillo, et al. Functional characterization of the mammalian mRNA decapping enzyme hDcp2. RNA. 2003 Sep;9(9):1138-47. [Content Brief]

[5]. Guowu Hu, et al. A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation regulates autophagy. Nat Cell Biol. 2015 Jul;17(7):930-942. [Content Brief]

[6]. Hao Wu, et al. Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs. Cell Rep. 2019 Dec 24;29(13):4422-4434.e13. [Content Brief]

[7]. Erwin van Dijk, et al. Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures. EMBO J. 2002 Dec 16;21(24):6915-24. [Content Brief]

[8]. Jens Lykke-Andersen, et al. Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Mol Cell Biol. 2002 Dec;22(23):8114-21. [Content Brief]

[9]. Fabrice Lejeune, et al. Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. Mol Cell. 2003 Sep;12(3):675-87. [Content Brief]

[10]. Thomas E Mullen, et al. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008 Jan 1;22(1):50-65. [Content Brief]

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