6ndk

Publication Abstract from PubMed

Modification of anticodon nucleotides allows tRNAs to decode multiple codons, expanding the genetic code. Additionally, modifications located in the anticodon loop, outside the anticodon itself, stabilize tRNA-codon interactions, increasing decoding fidelity. Anticodon loop nucleotide 37 is 3' to the anticodon and, in tRNACGGPro, is methylated at the N1 position in its nucleobase (m(1)G37). The m(1)G37 modification in tRNACGGPro stabilizes its interaction with the codon and maintains the mRNA frame. However, it is unclear how m(1)G37 affects binding at the decoding center to both cognate and +1 slippery codons. Here, we show that the tRNACGGProm(1)G37 modification is important for the association step during binding to a cognate CCG codon. In contrast, m(1)G37 prevented association with a slippery CCC-U or +1 codon. Similar analyses of frameshift suppressor tRNA(SufA6), a tRNACGGPro derivative containing an extra nucleotide in its anticodon loop that undergoes +1 frameshifting, reveal that m(1)G37 destabilizes interactions with both the cognate CCG and slippery codons. One reason for this destabilization is the disruption of a conserved U32.A38 nucleotide pairing in the anticodon stem through insertion of G37.5. Restoring the tRNA(SufA6) U32.A37.5 pairing results in a high-affinity association on the slippery CCC-U codon. Further, an X-ray crystal structure of the 70S ribosome bound to tRNA(SufA6) U32.A37.5 at 3.6 A resolution shows a reordering of the anticodon loop consistent with the findings from the high-affinity measurements. Our results reveal how the tRNA modification at nucleotide 37 stabilizes interactions with the mRNA codon to preserve the mRNA frame.

Importance of a tRNA anticodon loop modification and a conserved, noncanonical anticodon stem pairing in tRNACGGProfor decoding,Nguyen HA, Hoffer ED, Dunham CM J Biol Chem. 2019 Apr 5;294(14):5281-5291. doi: 10.1074/jbc.RA119.007410. Epub, 2019 Feb 19. PMID:30782843^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.