Phosphatase Subfamily RNGTT
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily RNGTT
RNGTT is an mRNA capping enzyme. The phosphatase domain removes the gamma phosphatase from the 5' end of new mRNAs, and a guanylyltransferase (GTase) domain adds GMP, which is then methylated by a separate enzyme (Wikipedia).
Evolution
RNGTT is ubiquitous in holozoa, and found in most other eukaryotic lineages as a multi-domain protein with both phosphatase and GTase activities (e.g. Arabidopsis NP_974263.1). Some clades, including Dictyostelium (XP_636333.1), Entamoeba and Phytophthora have replaced the RNGTT phosphatase domain with a phosphatase of the CYTH-like fold, but maintain the GTase domains. Many fungi have further separated the protein into a CYTH-like (Pfam:PF02940) phosphatase protein (CET1 in S. cerevisiae) [1, 2] and a separate GTase (CEG1 in S. cerevisiase) [3]
The RNGTT domain is highly divergent from other DSPs, but is closest to DSP11, the other RNA phosphatase.
Domain
Holozoan RNGTT has three conserved regions: an N-terminal phosphatase domain, a guanylyltransferase (GTase) domain that adds GMP (mRNA_cap_enzyme), and C-terminal conserved region (mRNA_cap_C).
Monosiga has second, a divergent RNGTT-like phosphatases (RNGTT-2) which lacks the GTase and C-terminal region, but has an N-terminal AB-hydolase domain, and this domain architecture is also seen in many fungi (e.g. Candida albicans KGU18713.1, Rhizopus microsporus EI89000.1, Neurospora crassa XP_011393974.1), and in Caspaspora (XP_004364216.2), and is similar to an algal protein that encodes only the phosphatase domain (e.g. Volvox carteri XP_002954283.1). Many of these species also have a more canonical RNGTT gene.
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) [2]. RNGTT carries out the first two steps through its phosphatase domain (RTase) and GTase domain.
References
- 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 |
- 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 |
