Targeting the Polyadenylation Signal of Pre-mRNA: A New Gene Silencing Approach for Facioscapulohumeral Dystrophy

International Journal of Molecular Sciences
Anne-Charlotte MarsollierJulie Dumonceaux

Abstract

Facioscapulohumeral dystrophy (FSHD) is characterized by the contraction of the D4Z4 array located in the sub-telomeric region of the chromosome 4, leading to the aberrant expression of the DUX4 transcription factor and the mis-regulation of hundreds of genes. Several therapeutic strategies have been proposed among which the possibility to target the polyadenylation signal to silence the causative gene of the disease. Indeed, defects in mRNA polyadenylation leads to an alteration of the transcription termination, a disruption of mRNA transport from the nucleus to the cytoplasm decreasing the mRNA stability and translation efficiency. This review discusses the polyadenylation mechanisms, why alternative polyadenylation impacts gene expression, and how targeting polyadenylation signal may be a potential therapeutic approach for FSHD.

References

Sep 16, 1976·Nature·N J Proudfoot, G G Brownlee
Nov 1, 1989·Genes & Development·Y TakagakiJ L Manley
Jul 25, 1995·Nucleic Acids Research·F ChenJ Wilusz
Jul 1, 1997·Molecular and Cellular Biology·Y Takagaki, J L Manley
Oct 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S M FlahertyG M Gilmartin
Nov 14, 1997·Genes & Development·D F Colgan, J L Manley
Sep 17, 1998·Nature·Y Hirose, J L Manley
Feb 12, 2000·Molecular and Cellular Biology·Y Takagaki, J L Manley
Jul 19, 2000·Genome Research·E BeaudoingD Gautheret
Jul 9, 2002·Molecular and Cellular Biology·Martha L PetersonFrankie Davis
May 30, 2003·The EMBO Journal·José Manuel Pérez Cañadillas, Gabriele Varani
Dec 24, 2003·Molecular Cell·Kirk M Brown, Gregory M Gilmartin
May 26, 2004·Biochimica Et Biophysica Acta·Uwe Kühn, Elmar Wahle
Oct 7, 2004·American Journal of Human Genetics·Richard J F L LemmersSilvere M van der Maarel
Jan 14, 2005·Nucleic Acids Research·Bin TianCarol S Lutz
Apr 7, 2005·RNA·João Paulo TavanezMaria Carmo-Fonseca
May 20, 2005·Current Opinion in Cell Biology·David L Bentley

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Citations

Jan 31, 2019·Nucleic Acids Research·Camille DionFrédérique Magdinier
Aug 1, 2020·Journal of Personalized Medicine·Eva SidlauskaiteJulie Dumonceaux
May 8, 2020·Acta Neuropathologica Communications·Albert Z HuangPoul H Sorensen
Dec 31, 2020·Journal of Personalized Medicine·Romains JoubertJulie Dumonceaux

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Methods Mentioned

BETA
antisense oligonucleotides
biopsies
antisense oligonucleotide
xenografts

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