Alternative titles; symbols
HGNC Approved Gene Symbol: RNGTT
Cytogenetic location: 6q15 Genomic coordinates (GRCh38) : 6:88,609,897-88,963,618 (from NCBI)
The RNGTT gene encodes capping enzyme, which initiates the formation of 5-prime-terminal caps on nascent pre-mRNAs through RNA 5-prime-triphosphatase and guanylyltransferase activities encoded in distinct domains (Yue et al., 1997; Yamada-Okabe et al., 1998).
By searching an EST database for sequences related to that of Pce1, the S. pombe guanylyltransferase, Yue et al. (1997) identified mouse cDNAs encoding Mce (mouse capping enzyme). Using an Mce cDNA as a probe, they screened a HeLa cell library and recovered a cDNA encoding RNGTT, the human homolog. The predicted 597-amino acid mouse and human proteins are 95% identical. The C-terminal regions of both proteins contain the conserved sequence motifs that identify members of the nucleotidyl transferase superfamily. The mouse enzyme exhibited both guanylyltransferase and RNA 5-prime-triphosphatase activities and bound selectively to the elongating form of RNA polymerase II, in which the largest subunit contains a phosphorylated C-terminal domain. The Mce gene complemented an S. cerevisiae ceg1 mutant strain. Yue et al. (1997) concluded that eukaryotic mRNA guanylyltransferases are conserved from yeast to mammals and that the phosphorylated C-terminal domain of RNA polymerase II couples capping to transcription elongation.
Independently, Tsukamoto et al. (1998) and Yamada-Okabe et al. (1998) cloned cDNAs encoding RNGTT, which they designated CAP1a and HCE1 (human capping enzyme-1), respectively. Using RT-PCR, Tsukamoto et al. (1998) demonstrated CAP1a expression in all human tissues tested.
Yamada-Okabe et al. (1998) found that recombinant HCE1 protein displayed RNA 5-prime-triphosphatase and guanylyltransferase activities and formed a cap structure at the 5-prime-triphosphate end of RNA. These authors also identified HCE1A and HCE1B, alternatively spliced mRNAs encoding proteins lacking part of the C-terminal region. The shorter isoforms possessed only RNA 5-prime-triphosphatase activity. HCE1, but not HCE1A or HCE1B, complemented S. cerevisiae ceg1 and cet1 mutations. Yamada-Okabe et al. (1998) concluded that the N-terminal part of HCE1 is responsible for RNA 5-prime-triphosphatase activity and the C-terminal part is essential for guanylyltransferase activity. RT-PCR analysis indicated that the level of HCE1 mRNA was significantly higher than those of HCE1A and HCE1B.
By analysis of somatic cell hybrid and radiation hybrid panels, Pillutla et al. (1998) mapped the RNGTT gene to chromosome 6q16.
Pillutla, R. C., Shimamoto, A., Furuichi, Y., Shatkin, A. J. Human mRNA capping enzyme (RNGTT) and cap methyltransferase (RNMT) map to 6q16 and 18p11.22-p11.23, respectively. Genomics 54: 351-353, 1998. [PubMed: 9828141] [Full Text: https://doi.org/10.1006/geno.1998.5604]
Tsukamoto, T., Shibagaki, Y., Murakoshi, T., Suzuki, M., Nakamura, A., Gotoh, H., Mizumoto, K. Cloning and characterization of two human cDNAs encoding the mRNA capping enzyme. Biochem. Biophys. Res. Commun. 243: 101-108, 1998. [PubMed: 9473487] [Full Text: https://doi.org/10.1006/bbrc.1997.8038]
Yamada-Okabe, T., Doi, R., Shimmi, O., Arisawa, M., Yamada-Okabe, H. Isolation and characterization of a human cDNA for mRNA 5-prime-capping enzyme. Nucleic Acids Res. 26: 1700-1706, 1998. [PubMed: 9512541] [Full Text: https://doi.org/10.1093/nar/26.7.1700]
Yue, Z., Maldonado, E., Pillutla, R., Cho, H., Reinberg, D., Shatkin, A. J. Mammalian capping enzyme complements mutant Saccharomyces cerevisiae lacking mRNA guanylyltransferase and selectively binds the elongating form of RNA polymerase II. Proc. Nat. Acad. Sci. 94: 12898-12903, 1997. [PubMed: 9371772] [Full Text: https://doi.org/10.1073/pnas.94.24.12898]