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Title

Cytosine-5 RNA methylation links protein synthesis to cell metabolism

AuthorsGkatza, Nikoletta A.; Castro, Cecilia; Harvey, Robert F.; Heiß, Matthias; C. Popis, Martyna; Blanco, Sandra
Issue Date14-Jun-2019
PublisherPublic Library of Science
CitationPLoS Biology 17(6): e3000297 (2019)
AbstractPosttranscriptional modifications in transfer RNA (tRNA) are often critical for normal development because they adapt protein synthesis rates to a dynamically changing microenvironment. However, the precise cellular mechanisms linking the extrinsic stimulus to the intrinsic RNA modification pathways remain largely unclear. Here, we identified the cytosine-5 RNA methyltransferase NSUN2 as a sensor for external stress stimuli. Exposure to oxidative stress efficiently repressed NSUN2, causing a reduction of methylation at specific tRNA sites. Using metabolic profiling, we showed that loss of tRNA methylation captured cells in a distinct catabolic state. Mechanistically, loss of NSUN2 altered the biogenesis of tRNA-derived noncoding fragments (tRFs) in response to stress, leading to impaired regulation of protein synthesis. The intracellular accumulation of a specific subset of tRFs correlated with the dynamic repression of global protein synthesis. Finally, NSUN2-driven RNA methylation was functionally required to adapt cell cycle progression to the early stress response. In summary, we revealed that changes in tRNA methylation profiles were sufficient to specify cellular metabolic states and efficiently adapt protein synthesis rates to cell stress.
Description© The Author(s).
Publisher version (URL)http://dx.doi.org/10.1371/journal.pbio.3000297
URIhttp://hdl.handle.net/10261/203042
DOI10.1371/journal.pbio.3000297
ISSN1544-9173
E-ISSN1545-7885
Appears in Collections:(IBMCC) Artículos
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