AI Article Synopsis
- * When specific splice site sequences are deleted, SRSF2 shifts its focus to alternative cryptic splice sites, even those with weaker associated sequences.
- * The activation of these cryptic splice sites by SRSF2 reduces the splicing from the typical sites, which decreases the inclusion of certain exons in the final RNA product.
Article Abstract
Here we show that the serine/arginine rich splicing factor 2 (SRSF2) promotes cryptic 3' splice-site (3'AG') usage during cassette exon exclusion in survival of motor neuron (SMN2) minigenes. Deletion of the 3'AG' (3'AG'1), its associated branch point (BP') and polypyrimidine tract (PPT') sequences directs SRSF2 to promote a second 3'AG' (3'AG'2) with less conserved associated region for intron splicing. Furthermore, deletion of both 3'AG'1 and 3'AG'2 and their associated sequences triggered usage of a third 3'AG'3 that has very weak associated sequences. Interestingly, when intron splicing was directed to the 3'AG' cryptic splice-sites, intron splicing from the canonical 3'AG splice-site was reduced along with a decrease in cassette exon inclusion. Moreover, multiple SRSF2 binding sites within the intron are responsible for 3'AG' activation. We conclude that SRSF2 facilitates exon exclusion by activating a cryptic 3'AG' and inhibiting downstream intron splicing.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678912 | PMC |
| http://dx.doi.org/10.3390/cells8070696 | DOI Listing |
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