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Publication : Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls.

First Author  Zhang C Year  2010
Journal  Science Volume  329
Issue  5990 Pages  439-43
PubMed ID  20558669 Mgi Jnum  J:165044
Mgi Id  MGI:4836113 Doi  10.1126/science.1191150
Citation  Zhang C, et al. (2010) Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science 329(5990):439-43
abstractText  The control of RNA alternative splicing is critical for generating biological diversity. Despite emerging genome-wide technologies to study RNA complexity, reliable and comprehensive RNA-regulatory networks have not been defined. Here, we used Bayesian networks to probabilistically model diverse data sets and predict the target networks of specific regulators. We applied this strategy to identify approximately 700 alternative splicing events directly regulated by the neuron-specific factor Nova in the mouse brain, integrating RNA-binding data, splicing microarray data, Nova-binding motifs, and evolutionary signatures. The resulting integrative network revealed combinatorial regulation by Nova and the neuronal splicing factor Fox, interplay between phosphorylation and splicing, and potential links to neurologic disease. Thus, we have developed a general approach to understanding mammalian RNA regulation at the systems level.
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