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Sex‐specific, reciprocal regulation of ER α and miR‐22 controls muscle lipid metabolism in male mice
Author(s) -
Schweisgut Judith,
Schutt Christian,
Wüst Stas,
Wietelmann Astrid,
Ghesquière Bart,
Carmeliet Peter,
Dröse Stefan,
Korach Kenneth S,
Braun Thomas,
Boettger Thomas
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695988
Subject(s) - biology , lipid metabolism , rna binding protein , microbiology and biotechnology , estrogen receptor , microrna , regulation of gene expression , rna , gene expression , metabolism , medicine , endocrinology , gene , genetics , cancer , breast cancer
Control of energy homeostasis and metabolism is achieved by integrating numerous pathways, and mi RNA s are involved in this process by regulating expression of multiple target genes. However, relatively little is known about the posttranscriptional processing of mi RNA s and a potential role for the precursors they derive from. Here, we demonstrate that mature mi RNA ‐22 is more abundant in muscle from male mice relative to females and that this enables sex‐specific regulation of muscular lipid metabolism and body weight by repressing estrogen receptor alpha ( ER α) expression. We found that the ER α adjusts its own activity by preventing processing of miR‐22 via direct binding to a conserved ER α‐binding element within the primary miR‐22 precursor. Mutation of the ER α binding site within the pri‐miR‐22 in vivo eliminates sex‐specific differences in miR‐22 expression. We reason that the resulting tissue selective negative feedback regulation is essential to establish sex‐specific differences in muscle metabolism and body weight development.