Abstract：
:Pre-mRNA splicing relies on the poorly understood dynamic interplay between >150 protein components of the spliceosome. The steps at which splicing can be regulated remain largely unknown. We systematically analyzed the effect of knocking down the components of the splicing machinery on alternative splicing events relevant for cell proliferation and apoptosis and used this information to reconstruct a network of functional interactions. The network accurately captures known physical and functional associations and identifies new ones, revealing remarkable regulatory potential of core spliceosomal components, related to the order and duration of their recruitment during spliceosome assembly. In contrast with standard models of regulation at early steps of splice site recognition, factors involved in catalytic activation of the spliceosome display regulatory properties. The network also sheds light on the antagonism between hnRNP C and U2AF, and on targets of antitumor drugs, and can be widely used to identify mechanisms of splicing regulation.
journal_name
Mol Celljournal_title
Molecular cellauthors
Papasaikas P,Tejedor JR,Vigevani L,Valcárcel Jdoi
10.1016/j.molcel.2014.10.030subject
Has Abstractpub_date
2015-01-08 00:00:00pages
7-22issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00865-Xjournal_volume
57pub_type
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