The development of the central nervous system (CNS) is a complex orchestration of stem cells, transcription factors, growth/differentiation factors, and epigenetic control. Noncoding RNAs have been identified, classified, and studied for their functional roles in many systems including the CNS. In particular, the class of long noncoding RNAs (lncRNAs) has generated both enthusiasm and skepticism due to the unexpected discovery, the diversity of mechanisms, and the lower level of expression than found in protein-coding RNAs. It is clear that lncRNAs exhibit a functional diversity that makes their study and compartmentalization more challenging than other classes of noncoding RNAs. The authors predict, however, that lncRNAs will be essential for the characterization of discrete neuronal cell types in the age of single-cell transcriptomics and that these regulatory RNAs contribute to the multitude of functional mechanisms during CNS differentiation that will rival the diversities of protein-based mechanisms.
Illustrated examples of lncRNA mechanisms
Among the many mechanisms used by lncRNAs during CNS development are: Interactions with transcription factors (TF), such as through decoy binding or competitive inhibition; Chromatin modulation by nucleosome displacement or chromatin looping; Recruitment of protein complexes to affect transcription or epigenetic regulation; Interaction with the translation machinery; mRNA stabilization; or Binding with microRNAs to interfere with their activity.