Summary information and primary citation
- PDB-id
-
5wnt;
DSSR-derived features in text and
JSON formats
- Class
- ribosome
- Method
- X-ray (3.3 Å)
- Summary
- Crystal structure of 30s ribosomal subunit from thermus
thermophilus
- Reference
-
Choi J, Indrisiunaite G, DeMirci H, Ieong KW, Wang J,
Petrov A, Prabhakar A, Rechavi G, Dominissini D, He C,
Ehrenberg M, Puglisi JD (2018): "2'-O-methylation
in mRNA disrupts tRNA decoding during translation
elongation." Nat. Struct. Mol. Biol.,
25, 208-216. doi: 10.1038/s41594-018-0030-z.
- Abstract
- Chemical modifications of mRNA may regulate many
aspects of mRNA processing and protein synthesis. Recently,
2'-O-methylation of nucleotides was identified as a
frequent modification in translated regions of human mRNA,
showing enrichment in codons for certain amino acids. Here,
using single-molecule, bulk kinetics and structural
methods, we show that 2'-O-methylation within coding
regions of mRNA disrupts key steps in codon reading during
cognate tRNA selection. Our results suggest that
2'-O-methylation sterically perturbs interactions of
ribosomal-monitoring bases (G530, A1492 and A1493) with
cognate codon-anticodon helices, thereby inhibiting
downstream GTP hydrolysis by elongation factor Tu (EF-Tu)
and A-site tRNA accommodation, leading to excessive
rejection of cognate aminoacylated tRNAs in initial
selection and proofreading. Our current and prior findings
highlight how chemical modifications of mRNA tune the
dynamics of protein synthesis at different steps of
translation elongation.
