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PMID: 26593421 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

RNA mis-splicing in disease.

Nature reviews. Genetics ·Vol. 17 ·No. 1 ·2016-01-00 ·Pages 19-32

Scotti MM, Swanson MS

Abstract

The human transcriptome is composed of a vast RNA population that undergoes further diversification by splicing. Detecting specific splice sites in this large sequence pool is the responsibility of the major and minor spliceosomes in collaboration with numerous splicing factors. This complexity makes splicing susceptible to sequence polymorphisms and deleterious mutations. Indeed, RNA mis-splicing underlies a growing number of human diseases with substantial societal consequences. Here, we provide an overview of RNA splicing mechanisms followed by a discussion of disease-associated errors, with an emphasis on recently described mutations that have provided new insights into splicing regulation. We also discuss emerging strategies for splicing-modulating therapy.

MeSH Terms
Alternative Splicing Animals Base Sequence Genetic Therapy Humans Muscular Dystrophy, Duchenne/genetics,metabolism,therapy Mutation Neoplasms/genetics,metabolism,therapy Protein Isoforms/genetics,metabolism RNA, Messenger/genetics,metabolism Spliceosomes/physiology
Chemicals
Protein Isoforms RNA, Messenger
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Scotti Marina M
Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida 32610-3610 USA.
Swanson Maurice S
Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida 32610-3610 USA.
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Article Info
Journal
Nature reviews. Genetics
Abbr.
Nat Rev Genet
ISSN
1471-0064
DOI
10.1038/nrg.2015.3
Published
2016-01-00
Epub
2015-00-23
Pages
19-32
Language
English
Region
England
NLM ID
100962779
PMCID
PMC5993438
Subset
IM
Grants
NIAMS NIH HHS · T32 AR7605‑15 · United States
NIAMS NIH HHS · R01 AR046799 · United States
NIAMS NIH HHS · AR046799 · United States
NIAMS NIH HHS · T32 AR007605 · United States
NINDS NIH HHS · P01 NS058901 · United States
NINDS NIH HHS · R01 NS098819 · United States
NINDS NIH HHS · NS058901 · United States
External Links
PubMed source DOI: 10.1038/nrg.2015.3 PMC Full Text View journal details
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