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.