Phosphatase Subfamily RNGTT
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily RNGTT
RNGTT is an mRNA capping enzyme found in holozoan.
Evolution
RNGTT is ubiquitous in holozoa, usually as a single-copy gene. As described in below, RNGTT has two distinct enzymatic domains: RNA triphosphatase and guanylyltransferase (GTase). In fungi, the two enzymatic activities are contained in separate but necessarily interacting proteins [1]. The GTase is conserved across eukaryotes; The phosphatase is found across eukaryotes including plants except fungi. Fungi have unique RNA triphosphatase distinct from that of RNGTT in other clades in sequence and structure [2, 3]. Thus, RNGTT emerged in early eukaryotes but lost in fungi perhaps through gene fission.
Domain
Holozoan RNGTT has three conserved regions: N-terminal phosphatase domain removing the gamma phosphate, guanylyltransferase (GTase) domain adding GMP, and C-terminal conserved region.
Function
RNGTT is an mRNA capping enzyme. Capping of nascent RNA 5′ ends is accomplished in eukaryotic cells and for most viruses in three sequential catalytic steps: removal of the gamma phosphate by RNA triphosphatase (RTase), addition of GMP from GTP by guanylyltransferase (GTase) via a phosphoamide linked GMP–enzyme intermediate, and N7 methylation of the added GMP by RNA (guanine-N7) methyltransferase (MTase) [3]. RNGTT carries out the first two steps through its phosphatase domain (RTase) and GTase domain.
References
- Ho CK, Lehman K, and Shuman S. An essential surface motif (WAQKW) of yeast RNA triphosphatase mediates formation of the mRNA capping enzyme complex with RNA guanylyltransferase. Nucleic Acids Res. 1999 Dec 15;27(24):4671-8. DOI:10.1093/nar/27.24.4671 |
- Lima CD, Wang LK, and Shuman S. Structure and mechanism of yeast RNA triphosphatase: an essential component of the mRNA capping apparatus. Cell. 1999 Nov 24;99(5):533-43. DOI:10.1016/s0092-8674(00)81541-x |
- Chu C, Das K, Tyminski JR, Bauman JD, Guan R, Qiu W, Montelione GT, Arnold E, and Shatkin AJ. Structure of the guanylyltransferase domain of human mRNA capping enzyme. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10104-8. DOI:10.1073/pnas.1106610108 |
