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      Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding

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          Abstract

          The ribosome is a molecular machine that converts genetic information in the form of RNA, into protein. Recent structural studies reveal a complex set of interactions between the ribosome and its ligands, mRNA and tRNA, that indicate ways in which the ribosome could avoid costly translational errors. Ribosomes must decode each successive codon accurately, and structural data provide a clear indication of how ribosomes limit recruitment of the wrong tRNA (sense errors). In a triplet-based genetic code there are three potential forward reading frames, only one of which encodes the correct protein. Errors in which the ribosome reads a codon out of the normal reading frame (frameshift errors) occur less frequently than sense errors, although it is not clear from structural data how these errors are avoided. Some mRNA sequences, termed programmed-frameshift sites, cause the ribosome to change reading frame. Based on recent work on these sites, this article proposes that the ribosome uses the structure of the codon–anticodon complex formed by the peptidyl-tRNA, especially its wobble interaction, to constrain the incoming aminoacyl-tRNA to the correct reading frame.

          Abstract

          How do ribosomes maintain translational reading frame? A new model suggests that the ribosome uses the structure of the P-site codon-anticodon complex to constrain reading to adjacent codons.

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          Most cited references25

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          RASMOL: biomolecular graphics for all

          R Sayle (1995)
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            Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity.

            J Hopfield (1974)
            The specificity with which the genetic code is read in protein synthesis, and with which other highly specific biosynthetic reactions take place, can be increased above the level available from free energy differences in intermediates or kinetic barriers by a process defined here as kinetic proofreading. A simple kinetic pathway is described which results in this proofreading when the reaction is strongly but nonspecifically driven, e.g., by phosphate hydrolysis. Protein synthesis, amino acid recognition, and DNA replication, all exhibit the features of this model. In each case, known reactions which otherwise appear to be useless or deleterious complications are seen to be essential to the proofreading function.
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              Signals for ribosomal frameshifting in the rous sarcoma virus gag-pol region

              The gag-pol protein of Rous sarcoma virus (RSV), the precursor to the enzymes responsible for reverse transcription and integration, is expressed from two genes that lie in different translational reading frames by ribosomal frameshifting. Here, we localize the site of frameshifting and show that the frameshifting reaction is mediated by slippage of two adjacent tRNAs by a single nucleotide in the 5′ direction. The gag terminator, which immediately follows the frameshift site, is not required for frameshifting. Other suspected retroviral frameshift sites mediate frameshifting when placed at the end of RSV gag. Mutations in RSV pol also affect synthesis of the gag-pol protein in vitro. The effects of these mutations best correlate with the potential to form an RNA stem-loop structure adjacent to the frameshift site. A short sequence of RSV RNA, 147 nucleotides in length, containing the frameshift site and stem-loop structure, is sufficient to direct frameshifting in a novel genetic context.
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                Author and article information

                Contributors
                Journal
                Trends Biochem Sci
                Trends Biochem. Sci
                Trends in Biochemical Sciences
                Elsevier Science Ltd.
                0968-0004
                0968-0004
                4 April 2002
                1 April 2002
                4 April 2002
                : 27
                : 4
                : 178-183
                Affiliations
                Dept of Biological Sciences and Program in Molecular and Cell Biology, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
                Author notes
                [* ]Corresponding author farabaug@ 123456umbc.edu
                Article
                S0968-0004(02)02064-9
                10.1016/S0968-0004(02)02064-9
                7126812
                11943544
                d3af0249-8a51-425e-b7e9-59c782ac189c
                Copyright © 2002 Elsevier Science Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Biochemistry
                ribosome,rrna,translational errors,programmed frameshifting,x-ray crystallography,wobble interactions

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