Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing.

ABSTRACT: Cellular gene expression machinery has coevolved with molecular parasites, such as viruses and transposons, which rely on host cells for their expression and reproduction. We previously reported that a wild-derived allele of mouse Nxf1 (Tap), a key component of the host mRNA nuclear export machinery, suppresses two endogenous retrovirus-induced mutations and shows suggestive evidence of positive selection. Here we show that Nxf1(CAST) suppresses a specific and frequent class of intracisternal A particle (IAP)-induced mutations, including Ap3d1(mh2J), a model for Hermansky-Pudlak syndrome, and Atcay(hes), an orthologous gene model for Cayman ataxia, among others. The molecular phenotype of suppression includes approximately two-fold increase in the level of correctly-spliced mRNA and a decr

SUBMITTER: Concepcion D 

PROVIDER: S-EPMC2674570 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature