Whole-genome RNAi screen identifies methylation-related genes influencing lipid metabolism in Caenorhabditis elegans

Xiaotong Zhu^{a, b},
Yangli Liu^{a, b},
Hong Zhang^{a, b},
Pingsheng Liu^{a, b
, ,}

a.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
b.
University of Chinese Academy of Sciences, Beijing 100049, China

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Corresponding author: E-mail address: pliu@ibp.ac.cn (Pingsheng Liu)

摘要

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Abstract: Lipid droplets (LDs) are highly conserved multifunctional cellular organelles and aberrant lipid storage in LDs can lead to many metabolic diseases. However, the molecular mechanisms governing lipid dynamic changes remain elusive, and the high-throughput screen of genes influencing LD morphology was limited by lacking specific LD marker proteins in the powerful genetic tool Caenorhabditis elegans. In this study, we established a new method to conduct whole-genome RNAi screen using LD resident protein DHS-3 as a LD marker, and identified 78 genes involved in significant LD morphologic changes. Among them, mthf-1, as well as a series of methylation-related genes, was found dramatically influencing lipid metabolism. SREBP-1 and SCD1 homologs in C. elegans were involved in the lipid metabolic change of mthf-1(RNAi) worms, and the regulation of ATGL-1 also contributed to it by decreasing triacylglycerol (TAG) hydrolysis. Overall, this study not only identified important genes involved in LD dynamics, but also provided a new tool for LD study usingC. elegans, with implications for the study of lipid metabolic diseases.
- Lipid droplet /
- RNAi screen /
- Lipid metabolism /
- One-carbon metabolism

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