Published online 5 May 2010 | Nature 465, 16-17 (2010) | doi:10.1038/465016a
The code within the code
Computational biologists grapple with RNA's complexity.
Heidi Ledford
One of the most beautiful aspects of the genetic code is its simplicity: three letters of DNA combine in 64 different ways, easily spelled out in a handy table, to encode the 20 standard amino acids that combine to form a protein.
Laguna Design - SPL - RNA: a difficult beast to predict
But between DNA and proteins comes RNA, and an expanding realm of complexity. RNA is a shape-shifter, sometimes carrying genetic messages and sometimes regulating them, adopting a multitude of structures that can affect its function. In a paper published in this issue (seepage 53), a team of researchers led by Benjamin Blencowe and Brendan Frey of the University of Toronto in Ontario, Canada, reports the first attempt to define a second genetic code: one that predicts how segments of messenger RNA transcribed from a given gene can be mixed and matched to yield multiple products in different tissues, a process called alternative splicing. This time there is no simple table — in its place are algorithms that combine more than 200 different features of DNA with predictions of RNA structure.
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Nature 465, 53-59 (6 May 2010) | doi:10.1038/nature09000; Received 9 December 2009; Accepted 9 March 2010
Deciphering the splicing code
Yoseph Barash1,2,4, John A. Calarco2,4, Weijun Gao1, Qun Pan2, Xinchen Wang1,2, Ofer Shai1, Benjamin J. Blencowe2 & Brendan J. Frey1,2,3
1. Biomedical Engineering, Department of Electrical and Computer Engineering, University of Toronto, 10 King’s College Road, Toronto M5S 3G4, Canada
2. Banting and Best Department of Medical Research and Department of Molecular Genetics, Donnelly Centre, University of Toronto, 160 College Street, Toronto M5S 3E1, Canada
3. Microsoft Research, 7 J. J. Thomson Avenue, Cambridge CB3 0FB, UK
4. These authors contributed equally to this work.
Correspondence to: Brendan J. Frey1,2,3 Email: frey@psi.toronto.edu
Correspondence to: Benjamin J. Blencowe2Email: b.blencowe@utoronto.ca
Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a ‘splicing code’, which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger RNA decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.
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NOTA DESTE BLOGGER:
Os pesquisadores não mencionaram a evolução darwiniana para explicar a origem e evolução deste código dentro de outro código, um exemplo de extrema complexidade biótica. Por que Darwin, aquele que teve a maior ideia que toda a humanidade já teve, quando chega na base fundamental da vida, ficou de fora?
Mero acaso? Fortuita necessidade? Ou Design Inteligente? Os termos teleológicos indicam ações inteligentes dentro do código dentro de outro código. Sinais de mudanças???
O tempora, o mores!!!
Mero acaso? Fortuita necessidade? Ou Design Inteligente? Os termos teleológicos indicam ações inteligentes dentro do código dentro de outro código. Sinais de mudanças???
O tempora, o mores!!!
