Natural Variant E610G Is a Semi-dominant Suppressor of IAP-Induced RNA Processing Defects

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Transposable elements, including endogenous retroviruses, have long been hypothesized as a substrate for creating or modulating gene regulatory networks, particularly through effects on transcription. However, several classes of elements are also known to affect alternative RNA processing events. We previously showed that the major allele of nuclear export factor Nxf1 in Mus musculus castaneus mice acts as a semi-dominant suppressor of de novo mutations caused by intracisternal A particle (IAP) endogenous retroviruses that integrate into introns, disrupting normal RNA processing. Here we show that this suppressor allele of Nxf1 can coordinately modify gene expression phenotypes at several endogenous loci in the C57BL/6 mouse reference genome that contain IAP sequences in their introns. This quadruples the number of known insertional events modified by Nxf1 and extends the effect beyond overt mutations. We previously used transgenic mice and viral vector mediated overexpression to demonstrate Nxf1 as the modifier gene for de novo insertions. Here we use direct genome editing in mouse one cell embryos to create custom germline alleles at the endogenous Nxf1 locus to show that a specific amino acid substitution, E610G, quantitatively accounts for the Nxf1 modifier gene activity.

Vyšlo v časopise: Natural Variant E610G Is a Semi-dominant Suppressor of IAP-Induced RNA Processing Defects. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005123
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005123

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