Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: AGO HITS-CLIP reveals distinct miRNA regulation of white and brown adipose tissue identity.

Authors: O'Connor, Sean; Murphy, Elisabeth A; Szwed, Sarah K; Kanke, Matt; Marchildon, François; Sethupathy, Praveen; Darnell, Robert B; Cohen, Paul

Published In Genes Dev, (2021 05 01)

Abstract: MicroRNAs (miRNAs) are short, noncoding RNAs that associate with Argonaute (AGO) to influence mRNA stability and translation, thereby regulating cellular determination and phenotype. While several individual miRNAs have been shown to control adipocyte function, including energy storage in white fat and energy dissipation in brown fat, a comprehensive analysis of miRNA activity in these tissues has not been performed. We used high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) to comprehensively characterize the network of high-confidence, in vivo mRNA:miRNA interactions across white and brown fat, revealing >20,000 unique AGO binding sites. When coupled with miRNA and mRNA sequencing, we found an inverse correlation between depot-enriched miRNAs and their targets. To illustrate the functionality of our HITS-CLIP data set in identifying specific miRNA:mRNA interactions, we show that miR-29 is a novel regulator of leptin, an adipocyte-derived hormone that coordinates food intake and energy homeostasis. Two independent miR-29 binding sites in the leptin 3' UTR were validated using luciferase assays, and miR-29 gain and loss of function modulated leptin mRNA and protein secretion in primary adipocytes. This work represents the only experimentally generated miRNA targetome in adipose tissue and identifies multiple regulatory pathways that may specify the unique identities of white and brown fat.

PubMed ID: 33832988 Exiting the NIEHS site

MeSH Terms: Adipocytes/cytology; Adipocytes/metabolism; Adipose Tissue/cytology*; Adipose Tissue/metabolism*; Animals; Argonaute Proteins/metabolism*; Binding Sites/genetics; Cells, Cultured; Chromatin Immunoprecipitation Sequencing*; Gene Expression Regulation*; Mice; Mice, Inbred C57BL; MicroRNAs/metabolism*; RNA, Messenger/metabolism

Back
to Top