RNGTT

RNGTT

RNGTT: Human RNA guanylyltransferase and 5’ -phosphatase
PDB Code: 2C46
Description
RNA triphosphatase catalyzes the hydrolysis of the gamma-phosphate of nascent pre-mRNA to form a diphosphate end which is subsequently capped with GMP by RNA guanyltransferase and methylated by (guanine-7) methyltransferase to yield mature m-RNA. These three enzymatic activities are present as separate polypeptides in yeasts. Metazoans including humans contain 2 genes: a separate cap methyltransferase (RNA guanine-7-methyltransferase, RNMT), and a bifunctional capping enzyme (RNGTT) encoded by a single gene exhibiting both RNA 5’-triphosphatase and guanylyltransferase activities.
RNGTTA contains an HCxxxxxR(S/T) motif typical for the cysteine phosphatase superfamily. RNA phosphatases are divided into two subgroups: The triphosphatase domains of bifunctional plant and metazoan capping enzymes which exclusively hydrolyze g-phosphates and monofunctional enzymes that convert RNA triphosphate ends to 5’ diphosphates and 5’ monophosphates.
Primary structures of RNA-specific phosphatases of different organisms show high sequence similarity but differ from other cysteine phosphatases outside the HCxxxxxR(S/T) motif.
RNA capping is essential for cell growth, and mutations of the triphosphatase, guanylyltransferase, or methyltransferase components of the capping apparatus that abrogate catalytic activity are lethal in vivo. The m7G cap facilitates translation initiation and failure to cap pre-mRNAs results in their accelerated decay by exo-ribonucleases.
Recently it has been shown that cap formation is an essential component of a transcription elongation checkpoint critical to HIV gene expression. Functional cap formation is stimulated in infected cells by HIV-Tat, a small RNA-binding protein required for efficient transcription of HIV genes. It has been shown that TAT i nteracts with RNGTTA and stimulates its guanylyltransferase and triphosphatase activitity suggesting that this complex contributes to the activation of HIV gene expression.

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