A strategy to analyze the phenotypic consequences of inhibiting the association of an RNA-binding protein with a specific RNA.

RNA
Marie CiboisLuc Paillard

Abstract

Targeted inactivations of RNA-binding proteins (RNA-BPs) can lead to huge phenotypical defects. These defects are due to the deregulation of certain mRNAs. However, we generally do not know, among the hundreds of mRNAs that are normally controlled by one RNA-BP, which are responsible for the observed phenotypes. Here, we designed an antisense oligonucleotide ("target protector") that masks the binding site of the RNA-BP CUG-binding protein 1 (CUGBP1) on the mRNA Suppressor of Hairless [Su(H)] that encodes a key player of Notch signaling. We showed that injecting this oligonucleotide into Xenopus embryos specifically inhibited the binding of CUGBP1 to the mRNA. This caused the derepression of Su(H) mRNA, the overexpression of Su(H) protein, and a phenotypic defect, loss of somitic segmentation, similar to that caused by a knockdown of CUGBP1. To demonstrate a causal relationship between Su(H) derepression and the segmentation defects, a rescue experiment was designed. Embryonic development was restored when the translation of Su(H) mRNA was re-repressed and the level of Su(H) protein was reduced to a normal level. This "target protector and rescue assay" demonstrates that the phenotypic defects associated with CUGBP1 inactivatio...Continue Reading

References

Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Isabel López de SilanesMyriam Gorospe
Oct 18, 2005·Molecular and Cellular Biology·Isabel López de SilanesMyriam Gorospe
Jun 6, 2006·Nature·Angélique GirardMichelle A Carmell
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Citations

Apr 10, 2014·ACS Applied Materials & Interfaces·Ana Cristina Norberto OliveiraMaria Elisabete Cunha Dias Real Oliveira
Aug 12, 2014·Nucleic Acids Research·Shungo AdachiTohru Natsume
Jul 16, 2010·Trends in Cell Biology·Marie CiboisLuc Paillard
Dec 20, 2011·Wiley Interdisciplinary Reviews. RNA·Twishasri Dasgupta, Andrea N Ladd
Sep 4, 2010·Biology of the Cell·Serge HardyLuc Paillard
Jan 19, 2013·Biochimica Et Biophysica Acta·Irina Vlasova-St LouisCarol J Wilusz
Jun 12, 2013·Nucleic Acids Research·John M EdwardsMark S Searle
May 5, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yotam Blech-HermoniAndrea N Ladd
Jul 15, 2015·Molecular and Cellular Biology·Gaella BoulangerLuc Paillard
Oct 6, 2017·FEMS Microbiology Reviews·Brice Felden, Luc Paillard

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