{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:14Z","timestamp":1790794514705,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["CA181572,CA184792,CA187956,CA214254,CA271443,"],"award-info":[{"award-number":["CA181572,CA184792,CA187956,CA214254,CA271443,"]}]},{"name":"National Institutes of Health","award":["CA296639."],"award-info":[{"award-number":["CA296639."]}]},{"name":"National Institutes of Health","award":["CA181572,CA184792,CA187956,CA214254,CA271443,"],"award-info":[{"award-number":["CA181572,CA184792,CA187956,CA214254,CA271443,"]}]},{"name":"National Institutes of Health","award":["CA296639."],"award-info":[{"award-number":["CA296639."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    Transfer RNA (tRNA) modifications play a critical role in regulating codon-specific mRNA translation and enabling tumor cell adaptation. The RNA methyltransferase 1 (METTL1) installs N7-methylguanosine (m\n                    <jats:sup>7<\/jats:sup>\n                    G) modifications on tRNAs, thereby shaping codon usage and translational output. However, the function and mechanistic contribution of the METTL1\/tRNA axis in pancreatic ductal adenocarcinoma (PDAC) remain poorly defined. Here, we showed that METTL1 was overexpressed in PDAC tissues and that elevated METTL1 expression was associated with poor patient survival. Genetic ablation of METTL1 markedly suppressed PDAC cell proliferation, migration, and tumor growth in vitro and in vivo. Mechanistically, METTL1 loss selectively reduced m\n                    <jats:sup>7<\/jats:sup>\n                    G-modified valine tRNAs \u2014 particularly Val-AAC, Val-CAC, and Val-TAC \u2014 leading to impaired translation of valine-enriched OXPHOS transcripts. As a consequence, METTL1 deficiency disrupted mitochondrial respiration and energy production in PDAC cells. Consistent with this model, valine tRNA levels were elevated in PDAC tissues, and their selective depletion phenocopied METTL1 loss by impairing mitochondrial bioenergetics and tumor cell fitness. Thus, the METTL1\/valine tRNA axis promoted PDAC progression through codon-dependent translational control of the mitochondrial electron transport chain and oxidative metabolism. Together, our findings identify a METTL1\/tRNA\/mitochondria signaling axis as a metabolic vulnerability and a promising therapeutic target in pancreatic cancer.\n                  <\/jats:p>","DOI":"10.1172\/jci204312","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:49:51Z","timestamp":1786470591000},"source":"Crossref","is-referenced-by-count":0,"title":["METTL1-mediated m7G modification of valine tRNAs drives metabolic adaptation in pancreatic ductal adenocarcinoma cells"],"prefix":"10.1172","volume":"136","author":[{"given":"Jiabei","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California, USA."},{"name":"Department of Clinical Laboratory, Shanghai Children\u2019s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Children\u2019s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhui","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Children\u2019s Medical Center, Shanghai Jiao Tong University School of Medicine, 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