Mutational analyses of trimethylguanosine synthase (Tgs1) and Mud2: proteins implicated in pre-mRNA splicing.

ABSTRACT: Yeast and human Tgs1 are orthologous RNA cap (guanine-N2) methyltransferases that convert m(7)G caps into the 2,2,7-trimethylguanosine (TMG) caps characteristic of spliceosomal snRNAs. TMG caps are dispensable for vegetative yeast growth, but are essential in the absence of Mud2, the putative yeast homolog of human splicing factor U2AF. Here we exploited the synthetic lethal interactions of tgs1Delta and mud2Delta mutations to identify essential structural features of the Tgs1 and Mud2 proteins. Thirty-two new mutations were introduced into human Tgs1 and surveyed for their effects on function in vivo in yeast and on the two sequential guanine-N2 methylation reactions in vitro. The structure-function data highlight a strictly essential pi-cation interaction between Trp766 and the m(7)G bas

SUBMITTER: Chang J 

PROVIDER: S-EPMC2856874 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature