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bioRxiv · 10.1101/540377

Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila

Sharma, A.·Akagi, K.·Kapahi, P.·Pattavina, B.·Wilson, K. A.·Nelson, C.·Watson, M.·Maksoud, E.·Ortega, M.·Brem, R.
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Abstract

Exposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish health span and accelerate aging. We have developed a Drosophila melanogaster model to study the molecular effects of radiation-induced damage and repair. Utilizing a quantitative intestinal permeability assay, we performed an unbiased GWAS screen (using [~]150 strains from the DGRP reference panel) to search for natural genetic variants that regulate radiation-induced gut permeability. From this screen, we identified the RNA binding protein, Musashi (msi).Msi overexpression promoted intestinal stem cell proliferation, which increased survival after irradiation and rescued radiation-induced gut permeability. We identified that a novel role of Msi in ISC proliferation a novel role for Msi in enhancing ISC function following radiation-induced gut damage, which identifies Msi as a potential therapeutic target.

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Sharma, A., Akagi, K., Kapahi, P., Pattavina, B., Wilson, K. A., Nelson, C., Watson, M., Maksoud, E., Ortega, M., Brem, R.. 2019-02-05. Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila. https://doi.org/10.1101/540377

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