Non-Syndromic Intellectual Disability and Its Pathways: A Long Noncoding RNA Perspective

Barros, Isabela Ichihara de; Leão, Vitor; Santis, Jessica Oliveira; Rosa, Reginaldo Cruz Alves; Brotto, Danielle Barbosa; Storti, Camila Baldin; Siena, Ádamo Davi Diógenes; Molfetta, Greice Andreotti de; Silva, Wilson A.

doi:10.3390/ncrna7010022

Cited by 3 publications

(2 citation statements)

References 183 publications

(221 reference statements)

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“…A large number of lncRNAs are differentially expressed during neural development and appear to be strongly linked to high-risk ID and ASD genes in co-expression networks [ 125 , 196 ], but very few have been molecularly and functionally characterized until now.…”

Section: The Search For Relevant Lncrnas Using Integrated Approachesmentioning

confidence: 99%

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

Liaci

Prandi

Pavinato

et al. 2022

IJMS

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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.

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Section: The Search For Relevant Lncrnas Using Integrated Approachesmentioning

confidence: 99%

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

Liaci

Prandi

Pavinato

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Considering the importance of lncRNAs in neuronal physiology it is not surprising that dysregulation of lncRNAs in the brain might be linked to neurodevelopmental disorders [ 160 , 161 ], autism spectrum disorders [ 162 , 163 , 164 ], substance use [ 165 ], intellectual disability [ 166 ], neurodegenerative diseases and neurological disorders [ 167 , 168 ]. A growing number of studies report that lncRNAs are associated with the pathology and development of neurodegenerative diseases [ 80 , 114 , 169 , 170 ].…”

Section: Lncrnas In Brain Disease and Neurodegeneration: Biomarkers Or Active Players?mentioning

confidence: 99%

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

2021

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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.

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Epigenetic insights into Fragile X Syndrome

Xie,

Li,

Xiao

et al. 2024

Front. Cell Dev. Biol.

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Fragile X Syndrome (FXS) is a genetic neurodevelopmental disorder closely associated with intellectual disability and autism spectrum disorders. The core of the disease lies in the abnormal expansion of the CGG trinucleotide repeat sequence at the 5′end of the FMR1 gene. When the repetition exceeds 200 times, it causes the silencing of the FMR1 gene, leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). Although the detailed mechanism by which the CGG repeat expansion triggers gene silencing is yet to be fully elucidated, it is known that this process does not alter the promoter region or the coding sequence of the FMR1 gene. This discovery provides a scientific basis for the potential reversal of FMR1 gene silencing through interventional approaches, thereby improving the symptoms of FXS. Epigenetics, a mechanism of genetic regulation that does not depend on changes in the DNA sequence, has become a new focus in FXS research by modulating gene expression in a reversible manner. The latest progress in molecular genetics has revealed that epigenetics plays a key role in the pathogenesis and pathophysiological processes of FXS. This article compiles the existing research findings on the role of epigenetics in Fragile X Syndrome (FXS) with the aim of deepening the understanding of the pathogenesis of FXS to identify potential targets for new therapeutic strategies.

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Non-Syndromic Intellectual Disability and Its Pathways: A Long Noncoding RNA Perspective

Cited by 3 publications

References 183 publications

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

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

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

Epigenetic insights into Fragile X Syndrome

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