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Alternative splicing

Deciding between the alternatives

Nature Reviews Genetics volume 10, page 71 (2009)Cite this article

Previously, the formation of stable protein–RNA complexes was thought to be important for splicing control element function. However, a new study by Yu et al. challenges this model. The authors used a randomization–selection approach to identify silencers within a pre-mRNA that contained two alternative 5′ splice sites: a weak upstream splice site and a strong proximal splice site. By looking for sequences that favoured the use of the weak splice site, they identified two exonic and four intronic motifs that functioned as strong splicing silencers both in vitro and in vivo. The authors only observed silencing when a competing upstream 5′ splice site was present. They concluded that the silencers did not work by sequestering or inactivating the strong splice site, but by altering competition between the two splice sites.

“...altered splicing patterns might be more important than expression changes in determining complex human traits.”

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References

ORIGINAL RESEARCH PAPERS

  1. Yu, Y. et al. Dynamic regulation of alternative splicing by silencers that modulate 5′ splice site competition. Cell 135, 1224–1236 (2008)

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  2. Heinzen E. L. et al. Tissue-specific genetic control of splicing: implications for the study of complex traits. PLoS Biol. 6, e1000001 (2008).

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FURTHER READING

  1. Wang, G.-S. & Cooper, T. A. Splicing in disease: disruption of the splicing code and the decoding machinery. Nature Rev. Genet. 8, 749–761 (2007).

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Authors
  1. Meera Swami
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Swami, M. Deciding between the alternatives. Nat Rev Genet 10, 71 (2009). https://doi.org/10.1038/nrg2532

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  • DOI: https://doi.org/10.1038/nrg2532

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