Fatty Acid Synthase Binds Cellular mRNAs and its Depletion Reduces Translational Efficiency
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,…
Recent research has uncovered the non-canonical RNA binding activity of metabolic enzymes, particularly fatty acid synthase (FASN), which holds implications for basic biology and disease. By employing crosslinking-based methods, scientists have characterized the direct RNA association of FASN in two human cell lines, revealing more than 6000 binding sites across over 3500 protein-coding genes. Remarkably, FASN exhibits a strong preference for the 5' untranslated region (UTR) of these genes.
To explore the functional consequences of FASN depletion, researchers conducted a functional cross-screen alongside ribosome profiling. The findings indicated that FASN depletion preferentially reduced the translational efficiencies of FASN-associated mRNAs. This effect was further shown to be dependent on the binding location and the number of binding sites within the mRNA. The associated transcripts were enriched for morphogenic and cell division-related functions, as well as palmitoylated proteins.
These results provide a compelling foundation for further investigation into FASN as a regulator of translation for its target mRNAs, with potential implications for understanding oncological and virological processes.
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