HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade.
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Cell Differentiation
/ physiology
Cell Line, Tumor
Epigenesis, Genetic
Gene Silencing
Heterogeneous-Nuclear Ribonucleoprotein K
/ genetics
Humans
MicroRNAs
/ genetics
Nerve Tissue Proteins
/ genetics
Neurons
/ cytology
Proteomics
/ methods
RNA-Binding Protein FUS
/ genetics
Transcription Factors
/ metabolism
Transfection
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
13 07 2020
13 07 2020
Historique:
received:
29
12
2019
accepted:
18
06
2020
revised:
15
06
2020
entrez:
15
7
2020
pubmed:
15
7
2020
medline:
16
4
2021
Statut:
epublish
Résumé
Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The sequential activation/repression of genes driving cell fate specification is achieved by complex regulatory networks, where transcription factors and noncoding RNAs work in a coordinated manner. Herein, we identify the long noncoding RNA HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1) as a new player in neuronal differentiation. We demonstrate that the neuronal-enriched HOTAIRM1 isoform epigenetically controls the expression of the proneural transcription factor NEUROGENIN 2 that is key to neuronal fate commitment and critical for brain development. We also show that HOTAIRM1 activity impacts on NEUROGENIN 2 downstream regulatory cascade, thus contributing to the achievement of proper neuronal differentiation timing. Finally, we identify the RNA-binding proteins HNRNPK and FUS as regulators of HOTAIRM1 biogenesis and metabolism. Our findings uncover a new regulatory layer underlying NEUROGENIN 2 transitory expression in neuronal differentiation and reveal a previously unidentified function for the neuronal-induced long noncoding RNA HOTAIRM1.
Identifiants
pubmed: 32661334
doi: 10.1038/s41419-020-02738-w
pii: 10.1038/s41419-020-02738-w
pmc: PMC7359305
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
FUS protein, human
0
Heterogeneous-Nuclear Ribonucleoprotein K
0
MicroRNAs
0
NEUROG2 protein, human
0
Nerve Tissue Proteins
0
RNA-Binding Protein FUS
0
Transcription Factors
0
long non-coding RNA HOTAIRM1, human
0
HNRNPK protein, human
146410-60-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
527Références
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