Alternative splicing (AS) of precursor mRNA (pre-mRNA) is a crucial step in the expression of most eukaryotic genes. Splicing factors (SFs) play an important role in AS regulation by binding to the cis-regulatory elements on the pre-mRNA. Although many splicing factors (SFs) and their binding sites have been identified, their combinatorial regulatory effects remain to be elucidated.
Now, researchers at the University of Miami have derived a biophysical model for AS regulation that integrates combinatorial signals of cis-acting splicing regulatory elements (SREs) and their interactions. They also developed a systematic framework for model inference. Applying the biophysical model to a human RNA-Seq data set, they demonstrate that their model can explain 49.1%-66.5% variance of the data, which is comparable to the best result achieved by biophysical models for transcription. These results show that this biophysical model and inference method provide a means of quantitative modeling of splicing regulation and is a useful tool for identifying SREs and their interactions.
Availability – The software package for model inference is available under an open source license.
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- Wen J, Chen Z, Cai X. (2013) A biophysical model for identifying splicing regulatory elements and their interactions. PLoS One 8(1), e54885. [article]