The role of neuronal specific splice factor, RBFOX1, in regulating circular RNA formation — ASN Events

The role of neuronal specific splice factor, RBFOX1, in regulating circular RNA formation (#152)

Akira Gokoolparsadh 1 , Jim Fang 1 , Christopher Pardy 1 , Irina Voineagu 1
  1. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney

Circular RNAs have emerged as a large class of non-coding RNA that may play potentially important roles in gene regulation. Showing remarkable enrichment in the mammalian brain, thousands of circRNAs are expressed at high levels and many are up-regulated during neurogenesis. To determine how the dynamic expression of circRNAs is achieved, it is critical to understand the key regulators of circRNA biogenesis. RNA binding proteins are trans-acting regulators that bind to the flanking introns to bridge the splice sites into close proximity, enhancing the back-splicing event. A neuronal specific splice factor, RBFOX1, implicated in autism spectrum disorder, has been shown to regulate both alternative splicing and transcriptional networks in human neuronal development. To investigate whether RBFOX1 regulates circular RNA formation in the brain, we over-expressed the splice factor in human primary astrocytes and observed a remarkable increase in circRNA abundance. The up-regulation of circRNAs was independent of the parental linear RNA. We found that RBFOX1-dependent circRNAs have long flanking introns harboring reverse complementary sequences that are known to promote circularization. Furthermore, RBFOX1-dependent circRNAs were found to significantly overlap circRNAs up-regulated during neuronal differentiation.

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