The control of lipid metabolism by mRNA splicing in Drosophila
Open accessAbstract
The storage of lipids is an evolutionarily conserved process that is important for the survival of organisms during shifts in nutrient availability. Triglycerides are stored in lipid droplets, but the mechanisms of how lipids are stored in these structures are poorly understood. Previous in vitro RNAi screens have implicated several components of the spliceosome in controlling lipid droplet formation and storage, but the in vivo relevance of these phenotypes is unclear. In this study, we identify specific members of the splicing machinery that are necessary for normal triglyceride storage in the Drosophila fat body. Decreasing the expression of the splicing factors U1-70K, U2AF38, U2AF50 in the fat body resulted in decreased triglyceride levels. Interestingly, while decreasing the SR protein 9G8 in the larval fat body yielded a similar triglyceride phenotype, its knockdown in the adult fat body resulted in a substantial increase in lipid stores. This increase in fat storage is due in part to altered splicing of the gene for the β-oxidation enzyme CPT1, producing an isoform with less enzymatic activity. Together, these data indicate a role for mRNA splicing in regulating lipid storage in Drosophila and provide a link between the regulation of gene expression and lipid homeostasis.
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A few of these non-canonical functions have been associated with lipid droplets in other organisms like Drosophila melanogaster and in other cell systems.
“Interestingly, a few of these non-canonical functions have been associated with lipid droplets in other organisms like Drosophila melanogaster46,66 and in other cell systems3,9.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [46]
The iPSC-derived astrocyte lipid droplet-associated proteome is enriched in non-canonical functions including spliceosome and antigen presentation.
“In addition to the canonical functions in lipid storage, the iPSC-derived astrocyte lipid droplet-associated proteome was enriched in non-canonical functions. These include functions related to the spliceosome, which has been previously linked to lipid droplet biology46, as well as antigen presentation.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [46]
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Research works printed but not linked: 22
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Cited by
Sorted by citations
Cuní-López, C., Root, J. T., Hao, Y., Blomberg, N., Koppes-den Hertog, S. J., Sacks, D., Trujillo, A. E., Ghirlando, R., Kowal, I., Epstein, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76565-6
- Authors
- Gingras, R. M., Warren, M. E., Nagengast, A. A., & DiAngelo, J. R.
- Affiliations
- Hofstra University (US)
- Widener University (US)
- Corresponding author
- Nagengast, Alexis A.
- DiAngelo, Justin R.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 443
- Issue
- 2
- Pages
- 672-676
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC4412844
- OpenAlex
- W2002885715
- Cited by
- 20
- References
- 0
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 1
- FWCI
- 0.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NSF
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- mRNA splicing, lipid metabolism, triglyceride storage, lipid droplets, fat body, Drosophila, spliceosome, U1-70K, carnitine palmitoyltransferase 1, fatty acid beta-oxidation, alternative splicing, lipid homeostasis
- MeSH terms
- Adipose Tissue, Animals, Drosophila, RNA Splicing, RNA, Messenger, RNA-Binding Proteins, Animals, Genetically Modified, Lipid Metabolism
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