ICLIP predicts the dual splicing effects of TIA-RNA interactions
Wang, Zhen (Author), Kayikci, Melis (Author), Briese, Michael (Author), Zarnack, Kathi (Author), Luscombe, Nicholas M. (Author), Rot, Gregor (Author), Zupan, Blaž (Author), Curk, Tomaž (Author), Ule, Jernej (Author)

URLURL - Presentation file, Visit http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000530 This link opens in a new window

The regulation of alternative splicing involves interactions between RNA-binding proteins and pre-mRNA positions close to the splice sites. T-cell intracellular antigen 1 (TIA1) and TIA1-like 1 (TIAL1) locally enhance exon inclusion by recruiting U1 snRNP to 5' splice sites. However, effects of TIA proteins on splicing of distal exons have not yet been explored. We used UV-crosslinking and immunoprecipitation (iCLIP) to find that TIA1 and TIAL1 bind at the same positions on human RNAs. Binding downstream of 5' splice sites was used to predict the effects of TIA proteins in enhancing inclusion of proximal exons and silencing inclusion of distal exons. The predictions were validated in an unbiased manner using splice-junction microarrays, RT-PCR, and minigene constructs, which showed that TIA proteins maintain splicing fidelity and regulate alternative splicing by binding exclusively downstream of 5' splice sites. Surprisingly, TIA binding at 5' splice sites silenced distal cassette and variable-length exons without binding in proximity to the regulated alternative 3' splice sites. Using transcriptome-wide high-resolution mapping of TIA-RNA interactions we evaluated the distal splicing effects of TIA proteins. These data are consistent with a model where TIA proteins shorten the time available for definition of an alternative exon by enhancing recognition of the preceding 5' splice site. Thus, our findings indicate that changes in splicing kinetics could mediate the distal regulation of alternative splicing.

Keywords:znotrajcelični antigen celic T, CLIP posameznih nukleotidov, uravnjavanje povezovanja, karta RNA
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FRI - Faculty of computer and information science
Number of pages:str. 1-16
Numbering:Vol. 8, no. 10
ISSN on article:1544-9173
COBISS.SI-ID:8022356 Link is opened in a new window
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Record is a part of a journal

Title:PLoS biology
Shortened title:PLoS biol.
Publisher:Public Library of Science
COBISS.SI-ID:512779289 This link opens in a new window

Secondary language

Keywords:T-cell intracellular antigen, individual-nucleotide CLIP, splicing regulation, RNA map

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