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

Meng Zhang,Boqin Qiang,Pengcheng Shu,Xiaozhong Peng,Li Jiao,Shuaiyao Lu,Bin Yin,Junjie Zhou,Longjiang Xu,Lin Hou

doi:10.3389/fnins.2021.709684

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.

Highlights

The mammalian neocortex is an evolved and complicated structure that is responsible for higherorder and complex brain physiological functions, such as cognition, sensory function, attention, memory, emotion, language, learning, motor function and perception
To investigate the T-uc.189 profile during mouse cerebral cortex development, we first detected the genomic location of T-uc.189, revealing that its UCR is located in the intronic region of the serine-arginine-rich splicing factor 3 (Srsf3) gene
T-uc.189 contained one open reading frame (ORF) encoding a putative protein of 129 amino acids that was identical to the predicted ORF of srsf3-204

Summary

Introduction

The mammalian neocortex is an evolved and complicated structure that is responsible for higherorder and complex brain physiological functions, such as cognition, sensory function, attention, memory, emotion, language, learning, motor function and perception. Mammalian neocortex formation, a complex and highly regulated developmental process, involves precise control of the differentiation and proliferation of neural progenitor cells (NPCs) (Kriegstein and Noctor, 2004; Evsyukova et al, 2013). The developing neocortex in the embryonic mouse brain contains the ventricular zone (VZ), subventricular zone (SV), intermediate zone (IZ) and cortical plate (CP). The orchestrated migration of newly generated neurons is the basis for the correct cortical hierarchy. The proliferation and differentiation of NPCs and the migration of neuronal cells are fundamental biological processes that underlie normal brain formation and function, and some neurological diseases and brain injuries are

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