Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops

• Type of Material: Article
• Authors: Tatsuya Maehigashi, Emory University; Jack A. Dunkle, Emory University; Stacey J. Miles, Emory University; Christine Dunham, Emory University
• Language: English
• Date: 2014-09-02
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: 2014 National Academy of Sciences
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1409436111
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• Volume: 111
• Issue: 35
• Start Page: 12740
• End Page: 12745
• Grant/Funding Information: Research reported in this publication was supported by National Institute of General Medical Sciences of the National Institutes of Health Grant R01GM093278 (to C.M.D.).; This work is based on research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines, which is supported by National Center for Research Resources National Institutes of Health Grant RR-15301, and the Southeast Regional Collaborative Access Team beamline.; Use of the Advanced Photon Source, an Office of Science User Facility operated for the US Department of Energy Office of Science by the Argonne National Laboratory, was supported by US Department of Energy Contract DE-AC02-06CH11357.
• Keywords: near cognate; TRANSFER-RNA; Science & Technology - Other Topics; READING FRAME MAINTENANCE; MUTANT; RIBOSOME; Science & Technology; 4-BASE CODONS; SUPPRESSOR GENE; processivity; RECOGNITION; TRANSLATION; Multidisciplinary Sciences; MUTATIONS; MESSENGER-RNA
• Research Categories: Chemistry, Biochemistry; Biology, Genetics

Abstract

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 tRNASufA6 and N1-methylguanosine at position 37 (m1G37) 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 tRNASufA6 to undergo a rearrangement of its 5′ stem that destabilizes U32, thereby disrupting the conserved U32-A38 base pair. Unexpectedly, the removal of the m1G37 modification of tRNAPro 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 themolecularmechanism behind suppressor tRNA-induced +1 frameshifting and advance our understanding of the role played by the ribosome in maintaining the correct translational reading frame.