“SR proteins and related factors play widespread roles in alternative pre-mRNA s

Question

“SR proteins and related factors play widespread roles in alternative pre-mRNA splicing and are known to promote splice site recognition through their Arg–Ser-rich effector domains. However, binding of SR regulators to some targets results in repression of splice sites through a distinct mechanism. Here, we investigate how activated and repressed targets of the Drosophila SR regulator Transformer2 elicit its differing effects on splicing. We find that, like activation, repression affects early steps in the recognition of splice sites and spliceosome assembly. Repositioning of regulatory elements reveals that Tra2 complexes that normally repress splicing from intronic positions activate splicing when located in an exon. Protein tethering experiments demonstrate that this position dependence is an intrinsic property of Tra2 and further show that repression and activation are mediated by separate effector domains of this protein. When other Drosophila SR factors (SF2 and Rbp1) that activate splicing from exonic positions were tethered intronically they failed to either activate or repress splicing. Interestingly, both activities of Tra2 favor the exonic identity of the RNA sequences that encompass its binding sites. This suggests a model in which these two opposite functions act in concert to define both the position and extent of alternatively spliced exons.

https://www.ncbi.nlm.nih.gov/pubmed/21914724

Is it possible for the activation and repression properties to work side by side to ensure the accuracy of the exon? If so, please explain

Explanation / Answer

SR proteins help in promoting the splice site recognition and helps in activation properties. However, the SR regulators bind to some target sites and leads repression of the splice sites. It was found that the recognition of the splice sites and the complete assembly of spliceosome is affected by repression. However, there is a possibility that both the activation and repression properties work together and helps in better axon accuracy. The Tra2 complex when used in the right way can help in gaining better axon accuracy. On placing the Tra2 complex within the exon it helps in activating the splicing along with the repression. There are different factors however which assist the Tra2 complex in working together both the repression and activation part. The SF2 factor together with Rbp1 was extracted and together placed in the exon position and it led to failed activation or repression. The binding of the SR proteins both in the exon area and the intron binding site together regulates both the activation and repression of exon to maintain the accuracy.

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