%0 Journal Article
%T Nxf1 Natural Variant E610G Is a Semi-dominant Suppressor of IAP-Induced RNA Processing Defects
%A Dorothy Concepcion&nbsp
%A Kevin D. Ross&nbsp
%A Kasey R. Hutt&nbsp
%A Gene W. Yeo&nbsp
%A Bruce A. Hamilton
%J PLOS Genetics
%D 2015
%I Public Library of Science (PLoS)
%R 10.1371/journal.pgen.1005123
%X Endogenous retroviruses and retrotransposons contribute functional genetic variation in animal genomes. In mice, Intracisternal A Particles (IAPs) are a frequent source of both new mutations and polymorphism across laboratory strains. Intronic IAPs can induce alternative RNA processing choices, including alternative splicing. We previously showed IAP I£¿1 subfamily insertional mutations are suppressed by a wild-derived allele of the major mRNA export factor, Nxf1. Here we show that a wider diversity of IAP insertions present in the mouse reference sequence induce insertion-dependent alternative processing that is suppressed by Nxf1CAST alleles. These insertions typically show more modest gene expression changes than de novo mutations, suggesting selection or attenuation. Genome-wide splicing-sensitive microarrays and gene-focused assays confirm specificity of Nxf1 genetic modifier activity for IAP insertion alleles. Strikingly, CRISPR/Cas9-mediated genome editing demonstrates that a single amino acid substitution in Nxf1, E610G, is sufficient to recreate a quantitative genetic modifier in a co-isogenic background.
%U http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1005123