Cells (Jul 2019)

Activation of Cryptic 3′ Splice-Sites by SRSF2 Contributes to Cassette Exon Skipping

  • Heegyum Moon,
  • Ha Na Jang,
  • Yongchao Liu,
  • Namjeong Choi,
  • Jagyeong Oh,
  • Jiyeon Ha,
  • Xuexiu Zheng,
  • Haihong Shen

DOI
https://doi.org/10.3390/cells8070696
Journal volume & issue
Vol. 8, no. 7
p. 696

Abstract

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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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