title: Induction of long noncoding RNA MALAT1 in hypoxic mice.
abstract: 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.
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Aurelia
authors: A
authors: Lelli
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Karen A
authors: KA
authors: Nolan
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Sara
authors: S
authors: Santambrogio
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Ana Filipa
authors: AF
authors: Gonçalves
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Miriam J
authors: MJ
authors: Schönenberger
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Anna
authors: A
authors: Guinot
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Ian J
authors: IJ
authors: Frew
authors: Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
authors: Hugo H
authors: HH
authors: Marti
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland; Institute of Physiology, University of Duisburg-Essen, Essen, Germany.
authors: David
authors: D
authors: Hoogewijs
authors: Institute of Physiology and Zurich Center for Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; National Center of Competence in Research "Kidney.CH", Zurich, Switzerland.
authors: Roland H
authors: RH
authors: Wenger
keywords: hypoxia-inducible factor; kidney; oxygen; proximal tubule; testis