Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops.
Publication Type:Journal Article
Source:Proc Natl Acad Sci U S A, Volume 111, Issue 35, p.12740-5 (2014)
Keywords:Anticodon, Crystallography, X-Ray, Escherichia coli, Frameshifting, Ribosomal, Genes, Suppressor, Inverted Repeat Sequences, Nucleic Acid Conformation, Ribosomes, RNA, Messenger, RNA, Transfer, Salmonella typhimurium, Thermus thermophilus
<p>Maintenance of the correct reading frame on the ribosome is essential for accurate protein synthesis. Here, we report structures of the 70S ribosome bound to frameshift suppressor tRNA(SufA6) and N1-methylguanosine at position 37 (m(1)G37) modification-deficient anticodon stem loop(Pro), both of which cause the ribosome to decode 4 rather than 3 nucleotides, resulting in a +1 reading frame. Our results reveal that decoding at +1 suppressible codons causes suppressor tRNA(SufA6) to undergo a rearrangement of its 5' stem that destabilizes U32, thereby disrupting the conserved U32-A38 base pair. Unexpectedly, the removal of the m(1)G37 modification of tRNA(Pro) also disrupts U32-A38 pairing in a structurally analogous manner. The lack of U32-A38 pairing provides a structural correlation between the transition from canonical translation and a +1 reading of the mRNA. Our structures clarify the molecular mechanism behind suppressor tRNA-induced +1 frameshifting and advance our understanding of the role played by the ribosome in maintaining the correct translational reading frame. </p>