Hedgehog Signaling Strength Is Orchestrated by the mir-310 Cluster of MicroRNAs in Response to Diet

Genetics
Ibrahim Ömer ÇiçekHalyna R Shcherbata

Abstract

Since the discovery of microRNAs (miRNAs) only two decades ago, they have emerged as an essential component of the gene regulatory machinery. miRNAs have seemingly paradoxical features: a single miRNA is able to simultaneously target hundreds of genes, while its presence is mostly dispensable for animal viability under normal conditions. It is known that miRNAs act as stress response factors; however, it remains challenging to determine their relevant targets and the conditions under which they function. To address this challenge, we propose a new workflow for miRNA function analysis, by which we found that the evolutionarily young miRNA family, the mir-310s (mir-310/mir-311/mir-312/mir-313), are important regulators of Drosophila metabolic status. mir-310s-deficient animals have an abnormal diet-dependent expression profile for numerous diet-sensitive components, accumulate fats, and show various physiological defects. We found that the mir-310s simultaneously repress the production of several regulatory factors (Rab23, DHR96, and Ttk) of the evolutionarily conserved Hedgehog (Hh) pathway to sharpen dietary response. As the mir-310s expression is highly dynamic and nutrition sensitive, this signal relay model helps to explain ...Continue Reading

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Citations

Feb 15, 2018·Physiological Reviews·Folami Y Ideraabdullah, Steven H Zeisel
Jan 24, 2018·Nature Communications·Mariya M Kucherenko, Halyna R Shcherbata
Nov 16, 2016·Journal of Neurogenetics·Alfredo GhezziNigel S Atkinson
Apr 27, 2020·Archives of Insect Biochemistry and Physiology·Umut ToprakGözde Güney
Feb 16, 2018·Journal of Cell Science·Mariya M Kucherenko, Halyna R Shcherbata
Apr 12, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Laure-Alix ClerbauxJennifer A Kennell
Nov 15, 2021·Molecular Ecology·Wei-Yun Lai, Christian Schlötterer

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Methods Mentioned

BETA
dissection
transgenic
PCR
GTPase
coimmunoprecipitation
GTPases

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