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Publication : HITS-CLIP yields genome-wide insights into brain alternative RNA processing.

First Author  Licatalosi DD Year  2008
Journal  Nature Volume  456
Issue  7221 Pages  464-9
PubMed ID  18978773 Mgi Jnum  J:143231
Mgi Id  MGI:3823192 Doi  10.1038/nature07488
Citation  Licatalosi DD, et al. (2008) HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456(7221):464-9
abstractText  Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.
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