Fatty Acid Synthase Binds Cellular mRNAs and its Depletion Reduces Translational Efficiency
- 1Vanderbilt University School of Medicine, Nashville, TN, USA
Abstract
Metabolic enzymes with non-canonical RNA binding activity have drawn a growing interest, due to their implications for basic biology and disease. Here we present the first endogenous RNA interactome of fatty acid synthase (FASN), an emerging oncological and virological target. Utilizing crosslinking-based approaches, we characterize the direct RNA association of FASN in two human cell lines, identifying over 6000 binding sites across over 3500 protein-coding genes, with a striking preference for the 5' UTR. We provide a functional cross-screen on the effects of FASN depletion on cellular translation. This integration with ribosome profiling indicated a preferential reduction in the translational efficiencies of FASN-associated mRNAs - an effect shown to be dependent on binding location and site number. Associated transcripts were enriched for morphogenic and cell division-related functions, as well as palmitoylated proteins. This correlative work primes further investigation of FASN as a regulator of translation of its target mRNAs.
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BibTeX
@misc{perevalovapinzul2026fatty,
title = {{Fatty Acid Synthase Binds Cellular mRNAs and its Depletion Reduces Translational Efficiency}},
author = {Y. Perevalova-Pinzul and J. Marks and M. P. Sajek and S. Clarke and S. Lisy and N. Mukherjee and S. Meydan and M. Ascano},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.764384},
url = {https://www.biorxiv.org/content/10.64898/2026.11.05.764384v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Fatty Acid Synthase Binds Cellular mRNAs and its Depletion Reduces Translational Efficiency
AU - Y. Perevalova-Pinzul
AU - J. Marks
AU - M. P. Sajek
AU - S. Clarke
AU - S. Lisy
AU - N. Mukherjee
AU - S. Meydan
AU - M. Ascano
PY - 2026
DA - 2026/11/05
PB - bioRxiv
DO - 10.64898/2026.11.05.764384
UR - https://www.biorxiv.org/content/10.64898/2026.11.05.764384v1
AB - Metabolic enzymes with non-canonical RNA binding activity have drawn a growing interest, due to their implications for basic biology and disease. Here we present the first endogenous RNA interactome of fatty acid synthase (FASN), an emerging oncological and virological target. Utilizing crosslinking-based approaches, we characterize the direct RNA association of FASN in two human cell lines, identifying over 6000 binding sites across over 3500 protein-coding genes, with a striking preference for the 5' UTR. We provide a functional cross-screen on the effects of FASN depletion on cellular translation. This integration with ribosome profiling indicated a preferential reduction in the translational efficiencies of FASN-associated mRNAs - an effect shown to be dependent on binding location and site number. Associated transcripts were enriched for morphogenic and cell division-related functions, as well as palmitoylated proteins. This correlative work primes further investigation of FASN as a regulator of translation of its target mRNAs.
ER -