Genomic analysis of wig-1 pathways.

PloS One
Yalda SedaghatBrett P Monia

Abstract

Wig-1 is a transcription factor regulated by p53 that can interact with hnRNP A2/B1, RNA Helicase A, and dsRNAs, which plays an important role in RNA and protein stabilization. in vitro studies have shown that wig-1 binds p53 mRNA and stabilizes it by protecting it from deadenylation. Furthermore, p53 has been implicated as a causal factor in neurodegenerative diseases based in part on its selective regulatory function on gene expression, including genes which, in turn, also possess regulatory functions on gene expression. In this study we focused on the wig-1 transcription factor as a downstream p53 regulated gene and characterized the effects of wig-1 down regulation on gene expression in mouse liver and brain. Antisense oligonucleotides (ASOs) were identified that specifically target mouse wig-1 mRNA and produce a dose-dependent reduction in wig-1 mRNA levels in cell culture. These wig-1 ASOs produced marked reductions in wig-1 levels in liver following intraperitoneal administration and in brain tissue following ASO administration through a single striatal bolus injection in FVB and BACHD mice. Wig-1 suppression was well tolerated and resulted in the reduction of mutant Htt protein levels in BACHD mouse brain but had no eff...Continue Reading

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Citations

Sep 7, 2013·Trends in Genetics : TIG·Nir Oksenberg, Nadav Ahituv
Nov 3, 2021·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Andreina FernandesRene Pareja

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Datasets Mentioned

BETA
GSE29751

Methods Mentioned

BETA
antisense oligonucleotides
transfection
PCR

Software Mentioned

Bioconductor
Ingenuity Pathway Analysis
Inegenuity Pathway Analysis
Siggenes
lumi
ImageJ

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