The Emerging Roles of Long Non-Coding RNAs in Intellectual Disability and Related Neurodevelopmental Disorders

Abstract

In the human brain, long non-coding RNAs (lncRNAs) are widely expressed in an exquisitely temporally and spatially regulated manner, thus suggesting their contribution to normal brain development and their probable involvement in the molecular pathology of neurodevelopmental disorders (NDD). Bypassing the classic protein-centric conception of disease mechanisms, some studies have been conducted to identify and characterize the putative roles of non-coding sequences in the genetic pathogenesis and diagnosis of complex diseases. However, their involvement in NDD, and more specifically in intellectual disability (ID), is still poorly documented and only a few genomic alterations affecting the lncRNAs function and/or expression have been causally linked to the disease endophenotype. Considering that a significant fraction of patients still lacks a genetic or molecular explanation, we expect that a deeper investigation of the non-coding genome will unravel novel pathogenic mechanisms, opening new translational opportunities. Here, we present evidence of the possible involvement of many lncRNAs in the etiology of different forms of ID and NDD, grouping the candidate disease-genes in the most frequently affected cellular processes in which ID-risk genes were previously collected. We also illustrate new approaches for the identification and prioritization of NDD-risk lncRNAs, together with the current strategies to exploit them in diagnosis.

New insights into RAGE/Diaph1 interaction as a modulator of actin cytoskeleton dynamics in peripheral nervous system in long‐term hyperglycaemia

“…LncRNA moesin pseudogene 1, antisense ( MSNP1AS ) may suppress the expression of cytoskeletal protein moesin in the celebral cortex (Liaci et al, 2022; Luo et al, 2020). Moesin is essential for neuronal morphogenesis, immunologic synapse formation and long‐term memory processing.…”

“…This cytoskeletal adaptor protein is crucial for maintaining proper actin cytoskeletal rearrangement in brain neurons (Figure 3; Freymuth & Fitzsimons, 2017). Studies indicated that the elevated expression of MSNP1AS may be correlated with the activation of RhoA signalling pathway (Liaci et al, 2022; Luo et al, 2020). Further, RhoA is correlated with Ras superfamily proteins, which are part of same biological signalling pathways, such as actin cytoskeletal integrity, cell proliferation, differentiation, adhesion, migration and apoptosis.…”

“…Studies revealed that s ynaptic Ras GTPase activating protein 1 (SYNGAP1) may slow down the process of neuritogenesis and RhoA cascade in neurons (Liaci et al, 2022). It is therefore likely that SYNGAP1 as well as lncRNA MSNP1AS are engaged in RhoA axis.…”