miR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar stimulation, inhibits Fos translation

Heon Jin Lee, M. Palkóvits, W. Scott Young

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The transcription factor activator protein 1 (AP-1) is formed through the dimerization of immediate-early genes Fos and Jun family members. Activator protein 1 is known as a pivotal regulator of major biological events such as cell proliferation, differentiation, organogenesis, memory formation, and apoptosis. During a search for microRNAs (miRNAs; small, endogenous, noncoding RNAs that repress gene expression of target mRNAs in animals posttranscriptionally) that are differentially expressed in the mouse paraventricular and supraoptic nuclei after 10 days of drinking 2% saline, one candidate microRNA that is relatively highly expressed, mmu-miR-7b (miR-7b), was studied further because sequence analysis suggested a likely interaction with the 3′ untranslated region of Fos mRNA, We show that miR-7b expression inhibits Fos translation in vitro and that it and its host gene are prominently expressed in the PVN and other brain areas, including the suprachiasmatic nucleus. No effect on Fos mRNA levels was observed. Normally, Fos is expressed at low to undetectable levels in cells, but it shows rapid induction and decay after acute stimuli. Various pathways have been identified through which Fos family proteins are degraded; our results indicate a significant additional mechanism by which Fos protein and activity may be regulated.

Original languageEnglish
Pages (from-to)15669-15674
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number42
DOIs
Publication statusPublished - Oct 17 2006

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MicroRNAs
Hypothalamus
Transcription Factor AP-1
Messenger RNA
Small Untranslated RNA
Supraoptic Nucleus
Suprachiasmatic Nucleus
Immediate-Early Genes
Organogenesis
Paraventricular Hypothalamic Nucleus
Dimerization
3' Untranslated Regions
Drinking
Sequence Analysis
Cell Differentiation
Proteins
Transcription Factors
Cell Proliferation
Apoptosis
Gene Expression

Keywords

  • AP-1
  • Hyperosmolality
  • Microarray
  • Paraventricular nucleus
  • Suprachiasmatic

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "miR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar stimulation, inhibits Fos translation",
abstract = "The transcription factor activator protein 1 (AP-1) is formed through the dimerization of immediate-early genes Fos and Jun family members. Activator protein 1 is known as a pivotal regulator of major biological events such as cell proliferation, differentiation, organogenesis, memory formation, and apoptosis. During a search for microRNAs (miRNAs; small, endogenous, noncoding RNAs that repress gene expression of target mRNAs in animals posttranscriptionally) that are differentially expressed in the mouse paraventricular and supraoptic nuclei after 10 days of drinking 2{\%} saline, one candidate microRNA that is relatively highly expressed, mmu-miR-7b (miR-7b), was studied further because sequence analysis suggested a likely interaction with the 3′ untranslated region of Fos mRNA, We show that miR-7b expression inhibits Fos translation in vitro and that it and its host gene are prominently expressed in the PVN and other brain areas, including the suprachiasmatic nucleus. No effect on Fos mRNA levels was observed. Normally, Fos is expressed at low to undetectable levels in cells, but it shows rapid induction and decay after acute stimuli. Various pathways have been identified through which Fos family proteins are degraded; our results indicate a significant additional mechanism by which Fos protein and activity may be regulated.",
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AU - Palkóvits, M.

AU - Young, W. Scott

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AB - The transcription factor activator protein 1 (AP-1) is formed through the dimerization of immediate-early genes Fos and Jun family members. Activator protein 1 is known as a pivotal regulator of major biological events such as cell proliferation, differentiation, organogenesis, memory formation, and apoptosis. During a search for microRNAs (miRNAs; small, endogenous, noncoding RNAs that repress gene expression of target mRNAs in animals posttranscriptionally) that are differentially expressed in the mouse paraventricular and supraoptic nuclei after 10 days of drinking 2% saline, one candidate microRNA that is relatively highly expressed, mmu-miR-7b (miR-7b), was studied further because sequence analysis suggested a likely interaction with the 3′ untranslated region of Fos mRNA, We show that miR-7b expression inhibits Fos translation in vitro and that it and its host gene are prominently expressed in the PVN and other brain areas, including the suprachiasmatic nucleus. No effect on Fos mRNA levels was observed. Normally, Fos is expressed at low to undetectable levels in cells, but it shows rapid induction and decay after acute stimuli. Various pathways have been identified through which Fos family proteins are degraded; our results indicate a significant additional mechanism by which Fos protein and activity may be regulated.

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