A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA

Area of Science:

• Genomics
• Neuroscience
• Developmental Biology

Background:

• Long non-coding RNAs (lncRNAs) are a diverse class of transcripts with significant expansion in primate brains.
• MicroRNAs (miRNAs) play crucial roles in post-transcriptional gene regulation.

Purpose of the Study:

• To identify and characterize novel lncRNAs involved in primate brain evolution.
• To investigate the function of a primate-specific lncRNA, LncND, in neural progenitor cells and its role in Notch signaling.

Main Methods:

• Bioinformatic analysis to identify lncRNAs with primate-specific features.
• In vitro studies using neuroblastoma cells and in vivo experiments in developing mouse cortex.
• Analysis of LncND expression in radial glia cells (RGCs) and its interaction with miR-143-3p.

Main Results:

• Identification of LncND, a primate-specific lncRNA with 16 binding sites for miR-143-3p.
• LncND regulates Notch receptor expression by binding and releasing miR-143-3p in neural progenitor cells.
• Downregulation of LncND reduced proliferation and induced neuronal differentiation in neuroblastoma cells.
• LncND gain-of-function expanded PAX6+ RGCs in the developing mouse cortex.

Conclusions:

• LncND is a key regulator of miRNA-mediated Notch signaling in primate neural progenitor cells.
• LncND may have played a role in the expansion of the primate cerebral cortex during evolution.