MicroRNA miR-7 Regulates Secretion of Insulin-Like Peptides

Pamela Agbu, Justin J. Cassidy, Jonathan Braverman, Alec Jacobson, Richard W. Carthew*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The insulin/insulin-like growth factor (IGF) pathway is essential for linking nutritional status to growth and metabolism. MicroRNAs (miRNAs) are short RNAs that are players in the regulation of this process. The miRNA miR-7 shows highly conserved expression in insulin-producing cells across the animal kingdom. However, its conserved functions in regulation of insulin-like peptides (ILPs) remain unknown. Using Drosophila as a model, we demonstrate that miR-7 limits ILP availability by inhibiting its production and secretion. Increasing miR-7 alters body growth and metabolism in an ILP-dependent manner, elevating circulating sugars and total body triglycerides, while decreasing animal growth. These effects are not due to direct targeting of ILP mRNA, but instead arise through alternate targets that affect the function of ILP-producing cells. The Drosophila F-actin capping protein alpha (CPA) is a direct target of miR-7, and knockdown of CPA in insulin-producing cells phenocopies the effects of miR-7 on ILP secretion. This regulation of CPA is conserved in mammals, with the mouse ortholog Capza1 also targeted by miR-7 in β-islet cells. Taken together, these results support a role for miR-7 regulation of an actin capping protein in insulin regulation, and highlight a conserved mechanism of action for an evolutionarily ancient microRNA.

Original languageEnglish (US)
Article numberbqz040
JournalEndocrinology (United States)
Volume161
Issue number2
DOIs
StatePublished - Feb 1 2020

Funding

We thank the Seung Kim Lab for generously providing us with the protocol, the reagents and the Drosophila stock to quantify stored and circulating dILP2HF. We additionally thank members of the Carthew and Beitel Labs for helpful discussions and advice. P.A. and J.J.C. were supported in part by the National Institutes of Health (NIH) Training Grant (T32GM008061). R.W.C. was supported by the National Institutes of Health (R35GM118144).

Keywords

  • Drosophila
  • growth
  • insulin
  • microRNA

ASJC Scopus subject areas

  • Endocrinology

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