tailieunhanh - Báo cáo khoa học: Alternative splicing: good and bad effects of translationally silent substitutions

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. | MINIREVIEW Alternative splicing good and bad effects of translationally silent substitutions M. Raponi and D. Baralle Academic Unit of Genetic Medicine Human Genetics Division University of Southampton Southampton General Hospital UK Keywords minigene NF1 pre-mRNA silent splicing translation Correspondence D. Baralle Academic Unit of Genetic Medicine Human Genetics Division University of Southampton Duthie Building Mailpoint 808 Southampton General Hospital Tremona Road Southampton SO16 6YD UK Fax 44 2380794346 Tel 44 2380796162 E-mail Received 26 August 2009 revised 4 November 2009 accepted 17 November 2009 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. doi Introduction Splicing is an important part of a post-transcriptional mechanism where introns are removed and exons are joined together allowing the resulting mature mRNA to be translated .

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