Induction of long noncoding RNA MALAT1 in hypoxic mice

Long thought to be “junk DNA”, in recent years it has become clear that a substantial fraction of intergenic genomic DNA is actually transcribed, forming long noncoding RNA (lncRNA). Like mRNA, lncRNA can also be spliced, capped, and polyadenylated, affecting a multitude of biological processes. Whi...

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Main Authors:	Lelli, Aurelia, Nolan, Karen A, Santambrogio, Sara, Gonçalves, Ana Filipa, Schönenberger, Miriam J, Guinot, Anna, Frew, Ian J, Marti, Hugo H, Hoogewijs, David, Wenger, Roland H
Format:	Online
Language:	English
Published:	Dove Medical Press 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045088/

id	pubmed-5045088
recordtype	oai_dc
spelling	pubmed-50450882016-10-21 Induction of long noncoding RNA MALAT1 in hypoxic mice Lelli, Aurelia Nolan, Karen A Santambrogio, Sara Gonçalves, Ana Filipa Schönenberger, Miriam J Guinot, Anna Frew, Ian J Marti, Hugo H Hoogewijs, David Wenger, Roland H Original Research Long thought to be “junk DNA”, in recent years it has become clear that a substantial fraction of intergenic genomic DNA is actually transcribed, forming long noncoding RNA (lncRNA). Like mRNA, lncRNA can also be spliced, capped, and polyadenylated, affecting a multitude of biological processes. While the molecular mechanisms underlying the function of lncRNAs have just begun to be elucidated, the conditional regulation of lncRNAs remains largely unexplored. In genome-wide studies our group and others recently found hypoxic transcriptional induction of a subset of lncRNAs, whereof nuclear-enriched abundant/autosomal transcript 1 (NEAT1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appear to be the lncRNAs most ubiquitously and most strongly induced by hypoxia in cultured cells. Hypoxia-inducible factor (HIF)-2 rather than HIF-1 seems to be the preferred transcriptional activator of these lncRNAs. For the first time, we also found strong induction primarily of MALAT1 in organs of mice exposed to inspiratory hypoxia. Most abundant hypoxic levels of MALAT1 lncRNA were found in kidney and testis. In situ hybridization revealed that the hypoxic induction in the kidney was confined to proximal rather than distal tubular epithelial cells. Direct oxygen-dependent regulation of MALAT1 lncRNA was confirmed using isolated primary kidney epithelial cells. In summary, high expression levels and acute, profound hypoxic induction of MALAT1 suggest a hitherto unrecognized role of this lncRNA in renal proximal tubular function. Dove Medical Press 2015-10-08 /pmc/articles/PMC5045088/ /pubmed/27774481 http://dx.doi.org/10.2147/HP.S90555 Text en © 2015 Lelli et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lelli, Aurelia Nolan, Karen A Santambrogio, Sara Gonçalves, Ana Filipa Schönenberger, Miriam J Guinot, Anna Frew, Ian J Marti, Hugo H Hoogewijs, David Wenger, Roland H
spellingShingle	Lelli, Aurelia Nolan, Karen A Santambrogio, Sara Gonçalves, Ana Filipa Schönenberger, Miriam J Guinot, Anna Frew, Ian J Marti, Hugo H Hoogewijs, David Wenger, Roland H Induction of long noncoding RNA MALAT1 in hypoxic mice
author_facet	Lelli, Aurelia Nolan, Karen A Santambrogio, Sara Gonçalves, Ana Filipa Schönenberger, Miriam J Guinot, Anna Frew, Ian J Marti, Hugo H Hoogewijs, David Wenger, Roland H
author_sort	Lelli, Aurelia
title	Induction of long noncoding RNA MALAT1 in hypoxic mice
title_short	Induction of long noncoding RNA MALAT1 in hypoxic mice
title_full	Induction of long noncoding RNA MALAT1 in hypoxic mice
title_fullStr	Induction of long noncoding RNA MALAT1 in hypoxic mice
title_full_unstemmed	Induction of long noncoding RNA MALAT1 in hypoxic mice
title_sort	induction of long noncoding rna malat1 in hypoxic mice
description	Long thought to be “junk DNA”, in recent years it has become clear that a substantial fraction of intergenic genomic DNA is actually transcribed, forming long noncoding RNA (lncRNA). Like mRNA, lncRNA can also be spliced, capped, and polyadenylated, affecting a multitude of biological processes. While the molecular mechanisms underlying the function of lncRNAs have just begun to be elucidated, the conditional regulation of lncRNAs remains largely unexplored. In genome-wide studies our group and others recently found hypoxic transcriptional induction of a subset of lncRNAs, whereof nuclear-enriched abundant/autosomal transcript 1 (NEAT1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appear to be the lncRNAs most ubiquitously and most strongly induced by hypoxia in cultured cells. Hypoxia-inducible factor (HIF)-2 rather than HIF-1 seems to be the preferred transcriptional activator of these lncRNAs. For the first time, we also found strong induction primarily of MALAT1 in organs of mice exposed to inspiratory hypoxia. Most abundant hypoxic levels of MALAT1 lncRNA were found in kidney and testis. In situ hybridization revealed that the hypoxic induction in the kidney was confined to proximal rather than distal tubular epithelial cells. Direct oxygen-dependent regulation of MALAT1 lncRNA was confirmed using isolated primary kidney epithelial cells. In summary, high expression levels and acute, profound hypoxic induction of MALAT1 suggest a hitherto unrecognized role of this lncRNA in renal proximal tubular function.
publisher	Dove Medical Press
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045088/
_version_	1613668380447866880

Induction of long noncoding RNA MALAT1 in hypoxic mice

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