Article

Alternative splicing: good and bad effects of translationally silent substitutions.

Academic Unit of Genetic Medicine, Human Genetics Division, University of Southampton, Southampton General Hospital, UK.
FEBS Journal (impact factor: 3.79). 02/2010; 277(4):836-40. DOI:10.1111/j.1742-4658.2009.07519.x pp.836-40
Source: PubMed

ABSTRACT Nucleotide variations that do not alter the protein-coding sequence have been routinely considered as neutral. In light of the developments we have seen over the last decade or so in the RNA processing and translational field, it would be proper when assessing these variants to ask if this change is neutral, good or bad. This question has been recently partly addressed by genome-wide in silico analysis but significantly fewer cases by laboratory experimental examples. Of particular relevance is the effect these mutations have on the pre-mRNA splicing pattern. In fact, alterations in this process may occur as a consequence of translationally silent mutations leading to the expression of novel splicing isoforms and/or loss of an existing one. This phenomenon can either generate new substrates for evolution or cause genetic disease when aberrant isoforms altering the essential protein function are produced. In this review we briefly describe the current understanding in the field and discuss emerging directions in the study of the splicing mechanism by integrating disease-causing splicing mutations and evolutionary changes.

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Keywords

aberrant isoforms altering
 
bad
 
cause genetic disease
 
current understanding
 
essential protein function
 
evolutionary changes
 
existing one
 
integrating disease-causing splicing mutations
 
laboratory experimental examples
 
last decade
 
mutations
 
novel splicing isoforms
 
Nucleotide variations
 
pre-mRNA splicing pattern
 
protein-coding sequence
 
RNA processing
 
silico analysis
 
splicing mechanism
 
translational field
 
translationally silent mutations