Functional Roles of Long Non-coding RNAs in Motor Neuron Development and Disease

Abstract

Long non-coding RNAs (lncRNAs) have gained increasing attention as they exhibit highly tissue-and cell-type specific expression patterns. LncRNAs are highly expressed in the central nervous system and their roles in the brain have been studied intensively in recent years, but their roles in the spinal motor neurons (MNs) are largely unexplored. Spinal MN development is controlled by precise expression of a gene regulatory network mediated spatiotemporally by transcription factors, representing an elegant paradigm for deciphering the roles of lncRNAs during development. Moreover, many MN-related neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are associated with RNA metabolism, yet the link between MN-related diseases and lncRNAs remains obscure. In this review, we summarize lncRNAs known to be involved in MN development and disease, and discuss their potential future therapeutic applications.

The Expression Discrepancy and Characteristics of Long Non-Coding RNAs in Peripheral Blood Leukocytes From Amyotrophic Lateral Sclerosis Patients

“…They are both associated with RNA metabolism and can produce cellular defects that can be the cause of ALS. Alteration of numerous lncRNAs has been described in different types of motor neuron diseases, however only very few of them have been subjected to in-depth studies of functions related to disease mechanisms [47]. The paraspeckle, a distinct cellular feature of ALS, was revealed that its formation connected with lncRNA NEAT1_2 which was reported association with ALS [32,48].…”

Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders

“…Within the nucleus, they can affect chromatin status through inter- and intra-chromosome interactions, remodeling chromatin and its condensation by acting on specific chromatin loci and regulating gene expression through mechanisms such as methylation or acetylation without changing the DNA sequence. Additionally, lncRNAs influence chromosome bridging by binding to heterogeneous nuclear ribonucleoprotein U [ 3 , 5 , 28 , 64 ]. A fraction of lncRNAs bind to the Polycomb repressive complex 1/2 (PRC1/2) [ 75 ] or the chromatin-modifying proteins CoREST and SMCX [ 76 ]; others bind to trithorax chromatin-activating complexes (trxG) [ 77 ].…”

“…LncRNAs can also act as scaffolds for higher-order complexes. For examples, lncRNAs can organize translational particles during ribosome translation in the endoplasmic reticulum (ER) [ 36 ] and to mediate stress granule formation through RNA–RNA interactions [ 5 ]. Finally, they can interact synergistically with mRNAs and act as miRNA inhibitory regulators modulating target expression [ 28 , 30 , 64 , 98 , 99 , 100 ].…”

“…ncRNAs are a heterogeneous group of genes that do not have functional open reading frames (ORFs) and are not transcribed into proteins. Due to these biological characteristics, for a long time, they were considered “junk” [ 4 , 5 ]. Recent data have shown that this part of the genome is functionally critical and is involved in physiological processes and tissue homeostasis [ 6 , 7 ] both in health and disease [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Genetics of familial amyotrophic lateral sclerosis

“…Считается, что БАС имеет мультифакторную природу. Точная этиология в настоящее время неизвестна, однако учеными описано множество патогенетических механизмов гибели мотонейронов при БАС: генетические факторы [4,5]; нарушение метаболизма и процессинга рибонуклеиновой кислоты (РНК) [6,7]; глутаматная эксайтотоксичность [8,9]; оксидативный стресс [10]; митохондриальная дисфункция [11][12][13]; поражение компонентов системы аксонального транспорта [14,15]; патологическая агрегация нейрофиламентов [16][17][18]; токсическая роль глиальных, дендритных, антиген-представляющих клеток [19]. В большинстве случаев БАС Bulletin of Siberian Medicine.…”