A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation

HOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell...

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Main Authors: Dana Segal, Samy Coulombe, Jasper Sim, Josée Dostie
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:RNA Biology
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Online Access:https://www.tandfonline.com/doi/10.1080/15476286.2023.2258028
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author Dana Segal
Samy Coulombe
Jasper Sim
Josée Dostie
author_facet Dana Segal
Samy Coulombe
Jasper Sim
Josée Dostie
author_sort Dana Segal
collection DOAJ
description HOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell model recapitulating their sequential induction during development. We found that it regulates 3’ HOXA gene expression by a mechanism involving epigenetic and three-dimensional chromatin changes. Here we show that HOTAIRM1 participates in proper progression through the early stages of neuronal differentiation. We found that it can associate with the HOXA1 transcription factor and contributes to its downstream transcriptional program. Particularly, HOTAIRM1 affects the NANOG/POU5F1/SOX2 core pluripotency network maintaining an undifferentiated cell state. HOXA1 depletion similarly perturbed expression of these pluripotent factors, suggesting that HOTAIRM1 is a modulator of this transcription factor pathway. Also, given that binding of HOTAIRM1 to HOXA1 was observed in different cell types and species, our results point to this ribonucleoprotein complex as an integral part of a conserved HOTAIRM1-HOXA1 regulatory axis modulating the transition from a pluripotent to a differentiated neuronal state.
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spelling doaj-art-b3613b91bd594c8ea80fc9da25d1f3ec2025-08-20T02:17:01ZengTaylor & Francis GroupRNA Biology1547-62861555-85842023-12-012011523153910.1080/15476286.2023.2258028A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiationDana Segal0Samy Coulombe1Jasper Sim2Josée Dostie3Department of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaDepartment of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaDepartment of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaDepartment of Biochemistry, and Rosalind & Morris Goodman Cancer Institute, McGill University, Montréal, Québec, CanadaHOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell model recapitulating their sequential induction during development. We found that it regulates 3’ HOXA gene expression by a mechanism involving epigenetic and three-dimensional chromatin changes. Here we show that HOTAIRM1 participates in proper progression through the early stages of neuronal differentiation. We found that it can associate with the HOXA1 transcription factor and contributes to its downstream transcriptional program. Particularly, HOTAIRM1 affects the NANOG/POU5F1/SOX2 core pluripotency network maintaining an undifferentiated cell state. HOXA1 depletion similarly perturbed expression of these pluripotent factors, suggesting that HOTAIRM1 is a modulator of this transcription factor pathway. Also, given that binding of HOTAIRM1 to HOXA1 was observed in different cell types and species, our results point to this ribonucleoprotein complex as an integral part of a conserved HOTAIRM1-HOXA1 regulatory axis modulating the transition from a pluripotent to a differentiated neuronal state.https://www.tandfonline.com/doi/10.1080/15476286.2023.2258028LncRNAHOXA1HOTAIRM1epigeneticschromatinpluripotency
spellingShingle Dana Segal
Samy Coulombe
Jasper Sim
Josée Dostie
A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation
RNA Biology
LncRNA
HOXA1
HOTAIRM1
epigenetics
chromatin
pluripotency
title A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation
title_full A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation
title_fullStr A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation
title_full_unstemmed A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation
title_short A conserved HOTAIRM1-HOXA1 regulatory axis contributes early to neuronal differentiation
title_sort conserved hotairm1 hoxa1 regulatory axis contributes early to neuronal differentiation
topic LncRNA
HOXA1
HOTAIRM1
epigenetics
chromatin
pluripotency
url https://www.tandfonline.com/doi/10.1080/15476286.2023.2258028
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