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Biomolecules. 2015 May 13;5(2):893-909. doi: 10.3390/biom5020893.

RNA-Binding Proteins: Splicing Factors and Disease.

Author information

1
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. alger_fredericks@brown.edu.
2
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. kamil_cygan@brown.edu.
3
Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Providence, RI 02912, USA. kamil_cygan@brown.edu.
4
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. b.anthony.brown830@gmail.com.
5
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, 70 Ship Street, Providence, RI 02903, USA. fairbrother@brown.edu.
6
Center for Computational Molecular Biology, Brown University, 115 Waterman Street, Providence, RI 02912, USA. fairbrother@brown.edu.

Abstract

Pre-mRNA splicing is mediated by interactions of the Core Spliceosome and an array of accessory RNA binding proteins with cis-sequence elements. Splicing is a major regulatory component in higher eukaryotes. Disruptions in splicing are a major contributor to human disease. One in three hereditary disease alleles are believed to cause aberrant splicing. Hereditary disease alleles can alter splicing by disrupting a splicing element, creating a toxic RNA, or affecting splicing factors. One of the challenges of medical genetics is identifying causal variants from the thousands of possibilities discovered in a clinical sequencing experiment. Here we review the basic biochemistry of splicing, the mechanisms of splicing mutations, the methods for identifying splicing mutants, and the potential of therapeutic interventions.

KEYWORDS:

RNA-binding proteins; motif; splicing

PMID:
25985083
PMCID:
PMC4496701
DOI:
10.3390/biom5020893
[Indexed for MEDLINE]
Free PMC Article

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