Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

Abstract

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling

“…During this cell cycle remodeling process triggered by the regulatory effects of CREB1 and JNK, environmental signaling for neurogenesis could be released. With the continuation of induction, the existence of an intermediate state allows the activation of neural development and damage repaired-related genes (NEAT1, MALAT1, ADARB1, NRG1, ZBTB20, PURA) [35][36][37][38][39][40]. The successful and continuous expression of the above intermediate state-related genes may provide the basis for successful FiNs reprogramming.…”

The Vulnerability of the Developing Brain: Analysis of Highly Expressed Genes in Infant C57BL/6 Mouse Hippocampus in Relation to Phenotypic Annotation Derived From Mutational Studies

“…On the contrary, this study was limited to protein coding genes and future work should include similar analyses on noncoding RNA (ncRNA) expression, such as microRNAs and long noncoding RNAs, as previous studies have shown that such RNAs are expressed in a tissue- and cell-specific manner, involved in neuronal differentiation and function, and implicated in various brain disorders. 88 - 95 However, although databases providing information on ncRNAs along with tissue expression profiles and predicted functions are now available as well as ncRNA knockout mouse models with reported phenotypes, 96 - 101 there is still a lack of databases that compiles the results from mutational studies and which also links the ncRNAs to phenotype in a similar way as the MGI’s Mammalian Phenotype database. Such databases would be of high value when further studying the roles of hippocampus.…”

Editorial: RNA at a breaking point? Cytoplasmic cleavage and other post-transcriptional RNA processing in neurodevelopment and disease

“…Regulatory RNAs, that include but are not limited to, long non-coding RNAs (lncRNA), microRNAs (miRNA) and circular RNAs (circRNAs), play crucial roles in various biological processes ranging from cell survival to specialized functions like target innervation. Such RNA species are often subjected to modifications, post-transcriptional processing, and are localized to different subcellular compartments, all of which contribute to their biological activity and specificity (Sambandan, 2017 ; Rajgor, 2020 ; Keihani et al, 2021 ; Samaddar and Banerjee, 2021 ; Zajaczkowski and Bredy, 2021 ). Lastly, mRNAs or their non-coding portions such as untranslated regions (UTRs) and introns can be bestowed with alternative functions independent of their coding potential and have been shown to modulate protein-protein interactions, intracellular signaling, subcellular localization and time-dependent expression (Nam et al, 2016 ; Andreassi et al, 2018 ; Huang, 2021 ).…”