biostudies-literatureKimbrough EMNIGMS NIH HHS7392https://www.ebi.ac.uk/biostudies/studies/S-EPMC12340085biostudies-literatureUnknown16(1)RNA post-transcriptional modifications act by stabilizing the functional conformations of RNA. While their role in messenger RNA (mRNA) decoding is well established, it is less clear how transfer RNA (tRNA) modifications outside the anticodon contribute to tRNA stability and accurate protein synthesis. Absence of such modifications causes translation errors, including mRNA frameshifting. By integrating single-molecule fluorescence resonance energy transfer and cryogenic electron microscopy, we demonstrate that the N¹-methylguanosine (m¹G) modification at position 37 of Escherichia coli tRNA^ProL is necessary and sufficient for modulating the conformational energy of this tRNA on the ribosome so as to suppress +1 frameshifting otherwise induced by this tRNA. Nature communicationsAn RNA modification prevents extended codon-anticodon interactions from facilitating +1 frameshifting.PMC12340085R35 GM153724R35 GM156629R01 GM093278R35 GM134931U24 GM129539R01 GM119386Li HDunham CMGamper HHou YMBailey NANguyen HAMattingly JMGonzalez RLKimbrough EMNing WfalseAn RNA modification prevents extended codon-anticodon interactions from facilitating +1 frameshifting.RNA post-transcriptional modifications act by stabilizing the functional conformations of RNA. While their role in messenger RNA (mRNA) decoding is well established, it is less clear how transfer RNA (tRNA) modifications outside the anticodon contribute to tRNA stability and accurate protein synthesis. Absence of such modifications causes translation errors, including mRNA frameshifting. By integrating single-molecule fluorescence resonance energy transfer and cryogenic electron microscopy, we demonstrate that the N¹-methylguanosine (m¹G) modification at position 37 of Escherichia coli tRNA^ProL is necessary and sufficient for modulating the conformational energy of this tRNA on the ribosome so as to suppress +1 frameshifting otherwise induced by this tRNA. 2025-01-01T00:00:00Z2025 Aug2026-07-15T12:41:28.081Z2026-07-04T03:14:46.764ZS-EPMC123400854078984810.1038/s41467-025-62342-4