Identification and epigenetic analysis of divergent long non-coding RNAs in multilineage differentiation of human Neural Progenitor Cells

Prajapati, Bharat; Fatma, Mena; Maddhesiya, Priya; Sodhi, Manjot Kour; Fatima, Mahar; Dargar, Tanushri; Bhagat, Reshma; Seth, Pankaj; Sinha, Subrata

doi:10.1080/15476286.2018.1553482

Cited by 15 publications

(12 citation statements)

References 36 publications

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“…Because downregulated HTTAS-v1 can be observed in HD brain sections, this NAT is thought to play a protective role in HD [7]. Certain microRNAs, including miR-214, miR-150, miR-146a and miR-125b, directly target the 3′UTR of both HTT and mHTT, which reduces HTT expression in human and mouse models [40,49]. These microRNAs protect neurons, and miR-146a, miR-150 and miR-125b are downregulated in the striatum of the commonly used HD model, R6/2 mice [41].…”

Section: Ncrnas In Hd Pathogenesismentioning

confidence: 99%

Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

2020

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Recent transcriptome analyses have revealed that noncoding RNAs (ncRNAs) are broadly expressed in mammalian cells and abundant in the CNS, with tissue and cell type-specific expression patterns. Moreover, ncRNAs have been found to intricately and dynamically regulate various signaling pathways in neurodegeneration. As such, some antisense transcripts and microRNAs are known to directly affect neurodegeneration in disease contexts. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/ mRNA that mediate these functions. Thus, further understanding of ncRNA biogenesis and effects might aid the discovery of diagnostic biomarkers or development of effective therapeutics for neurodegenerative disorders. Here, we review the ncRNAs that have so far been identified in major neurodegenerative disease etiology and the mechanisms that link ncRNAs with disease-specific phenotypes, such as HTT aggregation in HD, α-synuclein in PD, and Aβ plaques and hyperphosphorylated Tau in AD. We also summarize the known lncRNA/miRNA/mRNA networks that participate in neurodegenerative diseases, and we discuss ncRNA-related treatments shown to delay disease onset and prolong lifespan in rodent models.

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Section: Ncrnas In Hd Pathogenesismentioning

confidence: 99%

Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

2020

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“…We have studied the expression of BASP1 and BASP1-AS1 transcripts during lineage-specific differentiation of hNPCs, following the pre-established protocol for hNPC maintenance and differentiation [21][22][23] ( Supplementary Fig. S8a-f).…”

Section: Basp1-as1 Regulates Expression Of Basp1 During the Neuronal mentioning

confidence: 99%

Temporal transcriptome analysis of neuronal commitment reveals the preeminent role of the divergent lncRNA biotype and a critical candidate gene during differentiation

et al. 2020

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lncRNA genes can be genic or "intergenic". "Genic" RNAs can be further divided into six biotypes. Through genomewide analysis of a publicly available data set on corticogenesis, we found that the divergent lncRNA (XH) biotype, comprising the lncRNA and the coding gene being in opposite directions in a head-to-head manner, was most prominent during neural commitment. Within this biotype, a coding gene/divergent RNA pair of the BASP1 gene and the uncharacterized RNA loc285696 (hitherto referred as BASP1-AS1) formed a major HUB gene during neuronal differentiation. Experimental validation during the in vitro differentiation of human neural progenitor cells (hNPCs) showed that BASP1-AS1 regulates the expression of its adjacent coding gene, BASP1. Both transcripts increased sharply on the first day of neuronal differentiation of hNPCs, to fall steadily thereafter, reaching very low levels in differentiated neurons. BASP1-AS1 RNA and the BASP1 gene formed a molecular complex that also included the transcription factor TCF12. TCF12 is coded by the DYX1 locus, associated with inherited dyslexia and neurodevelopmental defects. Knockdown of BASP1-AS1, BASP1, or TCF12 impaired the neuronal differentiation of hNPCs, as seen by reduction in DCX and TUJ1-positive cells and by reduced neurite length. There was also increased cell proliferation. A common set of critical genes was affected by the three molecules in the complex. Our study thus identified the role of the XH biotype and a novel mediator of neuronal differentiation-the complex of BASP1-AS1, BASP1, and TCF12. It also linked a neuronal differentiation pathway to inherited dyslexia.

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“…A similar case can be construed during development for nervous system specification. Recently, among other functions, lncRNAs that overlap genes but are transcribed in the opposite direction, place critical roles in the differentiation of nervous system subtypes . In general, several considerations have been garnered from both in vitro and in vivo studies using neuronal populations, stem cells, dissected neuronal tissue types, and even single cell RNA‐seq.…”

Section: Nervous System Developmentmentioning

confidence: 99%

“…Recently, among other functions, lncRNAs that overlap genes but are transcribed in the opposite direction, place critical roles in the differentiation of nervous system subtypes. 70 In general, several considerations have been garnered from both in vitro and in vivo studies using neuronal populations, stem cells, dissected neuronal tissue types, and even single cell RNA-seq. The number of lncRNAs has increased significantly with brain complexity, and has "sky-rocketed" in the human brain.…”

Section: Nervous System Developmentmentioning

confidence: 99%

The various and shared roles of lncRNAs during development

Murillo‐Maldonado

Riesgo-Escovar

2019

Developmental Dynamics

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lncRNAs, genes transcribed but not translated, longer than 200 nucleotides, are classified as a separate class of nonprotein coding genes. Since their discovery, largely from RNAseq data, a number of pioneer studies have begun to unravel its myriad functions, centered on gene expression regulation, suggesting developmental and evolutionary conservation. Since they do not code for proteins and have no open reading frames, their functional constraints likely differ from that of protein coding genes, or of genes where the majority of the nucleotide sequence is required for function, like tRNAs. This has complicated assessment of both developmental and evolutionary conservation, and the identification of homologs in different species. Here we argue that other characteristics: general synteny and particular chromosomal placement regardless of sequence, sequence micro‐motifs, and secondary structure allow for “homologs” to be identified and compared, confirming developmental and evolutionary conservation of lncRNAs. We conclude exemplifying a case in point: that of the evolutionarily conserved lncRNA acal, characterized and required for embryogenesis in Drosophila.

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Identification and epigenetic analysis of divergent long non-coding RNAs in multilineage differentiation of human Neural Progenitor Cells

Cited by 15 publications

References 36 publications

Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

Temporal transcriptome analysis of neuronal commitment reveals the preeminent role of the divergent lncRNA biotype and a critical candidate gene during differentiation

The various and shared roles of lncRNAs during development

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