Long Non-coding RNA T-uc.189 Modulates Neural Progenitor Cell Fate by Regulating Srsf3 During Mouse Cerebral Cortex Development

Abstract

Neurogenesis is a complex process that depends on the delicate regulation of spatial and temporal gene expression. In our previous study, we found that transcribed ultra-conserved regions (T-UCRs), a class of long non-coding RNAs that contain UCRs, are expressed in the developing nervous systems of mice, rhesus monkeys, and humans. In this study, we first detected the full-length sequence of T-uc.189, revealing that it was mainly concentrated in the ventricular zone (VZ) and that its expression decreased as the brain matured. Moreover, we demonstrated that knockdown of T-uc.189 inhibited neurogenesis. In addition, we found that T-uc.189 positively regulated the expression of serine-arginine-rich splicing factor 3 (Srsf3). Taken together, our results are the first to demonstrate that T-uc.189 regulates the expression of Srsf3 to maintain normal neurogenesis during cortical development.

Transcribed-Ultra Conserved Regions (T-UCRs) a New Light on a Dark Matter

“…Another interesting regulatory mechanism exercised by T-UCRs was presented by Zhang et al [27]. The authors revealed a new regulatory relationship between T-UCRs and their host genes.…”

“…The authors revealed a new regulatory relationship between T-UCRs and their host genes. They suggested that uc.189 positively regulates the expression of the splicing factor SRp20, but did not provide any mechanistic evidence to explain how this occurs [27].…”

Ultra-conserved RNA: a novel biological tool with diagnostic and therapeutic potential

“…It has been reported that the ucRNA, uc.189, promotes the development of the neocortex by limiting its expression to the ventricular zone (VZ) which is located in the nucleus. It was also identified the ucRNA, uc.189, can upregulate its regulatory target serine-arginine-rich splicing factor 3 (SRSF3) protein expression, which prevents the abnormal proliferation of neural progenitor cells [ 5 ]. E60UCS is important for brain development.…”