TY - JOUR
T1 - Identification and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2)
AU - Scott, Hamish S.
AU - Antonarakis, Stylianos E.
AU - Lalioti, Maria D.
AU - Rossier, Colette
AU - Silver, Pamela A.
AU - Henry, Michael F.
N1 - Funding Information:
We thank the following investigators for providing puri®ed proteins: Adrian Krainer, Akila Mayeda, and Ethan Ford for Npl3p and hnRNPA1; Claire Moore and Marco Kessler for Rna15p and Pabp; and Michael Tyo for human MBP. This work was funded by grants from the Swiss FNRS (31.33965.92 and 31-40500.94) and the EU/ OFES (CT93-0015) and by funds from the University and Cantonal Hospital of Geneva to S.E.A. and from the NIH to P.A.S., by a C. J. Martin Fellowship from the National Health and Medical Research Council of Australia (957348) to H.S.S., and by an ACS postdoctoral fellowship to M.F.H. M.D.L. is a trainee of the Graduate Program of Molecular and Cellular Biology of the University of Geneva Medical School.
PY - 1998/3/15
Y1 - 1998/3/15
N2 - RNA-binding proteins such as heterogeneous nuclear ribonucleoproteins (hnRNPs), which contain the bulk of methylated arginine residues in eukaryotic cells, play many essential roles in the metabolism of nuclear pre- mRNA. Arginine methyltransferase activity has also been implicated in signal transduction events with components of the cellular growth and viral response pathways. We recently characterized a single yeast hnRNP methyltransferase (HMT1). We now present the identification and characterization of two putative human arginine methyltransferases termed HRMT1L1 and HRMT1L2. In addition to methyltransferase similarities, the N-terminal region of the HRMT1L1 protein contains an Src homology 3 domain. HRMT1L1 maps to a YAC containing the telomere of chromosome 21q. Three alternatively spliced HRMT1L2 transcripts with variable 5'-ends were observed, encoding proteins of 343, 347, and 361 amino acids, respectively. HRMT1L2 maps to human chromosome 19q. Recombinant HRMT1L2 protein encoded by the most common 5'-variant exhibited methyltransferase activity in vitro. Furthermore, in vivo activity was demonstrated by complementation of a yeast HMT1 mutant strain. The identification of highly conserved Hmt1p human homologues that function in yeast indicates that analyses of this class of enzymes in yeast may be directly applicable to higher eukaryotes. The possible roles of HRMT1L1 and HRMT1L2 in human disease are currently unknown.
AB - RNA-binding proteins such as heterogeneous nuclear ribonucleoproteins (hnRNPs), which contain the bulk of methylated arginine residues in eukaryotic cells, play many essential roles in the metabolism of nuclear pre- mRNA. Arginine methyltransferase activity has also been implicated in signal transduction events with components of the cellular growth and viral response pathways. We recently characterized a single yeast hnRNP methyltransferase (HMT1). We now present the identification and characterization of two putative human arginine methyltransferases termed HRMT1L1 and HRMT1L2. In addition to methyltransferase similarities, the N-terminal region of the HRMT1L1 protein contains an Src homology 3 domain. HRMT1L1 maps to a YAC containing the telomere of chromosome 21q. Three alternatively spliced HRMT1L2 transcripts with variable 5'-ends were observed, encoding proteins of 343, 347, and 361 amino acids, respectively. HRMT1L2 maps to human chromosome 19q. Recombinant HRMT1L2 protein encoded by the most common 5'-variant exhibited methyltransferase activity in vitro. Furthermore, in vivo activity was demonstrated by complementation of a yeast HMT1 mutant strain. The identification of highly conserved Hmt1p human homologues that function in yeast indicates that analyses of this class of enzymes in yeast may be directly applicable to higher eukaryotes. The possible roles of HRMT1L1 and HRMT1L2 in human disease are currently unknown.
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U2 - 10.1006/geno.1997.5190
DO - 10.1006/geno.1997.5190
M3 - Article
C2 - 9545638
AN - SCOPUS:0032521176
SN - 0888-7543
VL - 48
SP - 330
EP - 340
JO - Genomics
JF - Genomics
IS - 3
ER -