Nonsense suppression by near-cognate tRNAs employs alternative base pairing at codon positions 1 and 3

Proceedings of the National Academy of Sciences of the United States of America
Bijoyita RoyAllan Jacobson

Abstract

Premature termination codons (PTCs) in an mRNA ORF inactivate gene function by causing production of a truncated protein and destabilization of the mRNA. Readthrough of a PTC allows ribosomal A-site insertion of a near-cognate tRNA, leading to synthesis of a full-length protein from otherwise defective mRNA. To understand the mechanism of such nonsense suppression, we developed a yeast system that allows purification and sequence analysis of full-length readthrough products arising as a consequence of endogenous readthrough or the compromised termination fidelity attributable to the loss of Upf (up-frameshift) factors, defective release factors, or the presence of the aminoglycoside gentamicin. Unlike classical "wobble" models, our analyses showed that three of four possible near-cognate tRNAs could mispair at position 1 or 3 of nonsense codons and that, irrespective of whether readthrough is endogenous or induced, the same sets of amino acids are inserted. We identified the insertion of Gln, Tyr, and Lys at UAA and UAG, whereas Trp, Arg, and Cys were inserted at UGA, and the frequency of insertion of individual amino acids was distinct for specific nonsense codons and readthrough-inducing agents. Our analysis suggests that the...Continue Reading

References

Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·Y X FengJ G Levin
Dec 20, 1986·Journal of Molecular Biology·W A Weiss, E C Friedberg
Mar 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·Y YoshinakaS Oroszlan
Jun 14, 1971·Journal of Molecular Biology·D Hirsh
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·K K McCaughanW P Tate
Nov 25, 1995·Nucleic Acids Research·C Urban, H Beier
Jan 1, 1996·Annual Review of Biochemistry·R F Gesteland, J F Atkins
Dec 28, 1999·Annual Review of Cell and Developmental Biology·T R Serio, S L Lindquist
Jun 10, 2000·Molecular and Cellular Biology·A B MaderazoA Jacobson
Jan 25, 2007·PloS One·Jennifer L Baxter-RoshekJonathan D Dinman
Jun 12, 2008·Annual Review of Microbiology·Elaine M YoungmanRachel Green
Feb 26, 2009·Cell·Hani S Zaher, Rachel Green
Jul 17, 2010·Genes & Development·Marcus J O Johansson, Allan Jacobson
Jun 6, 2012·Nature Structural & Molecular Biology·Christopher J Shoemaker, Rachel Green
Oct 18, 2012·Nature Reviews. Molecular Cell Biology·Stephanie Kervestin, Allan Jacobson
Dec 12, 2012·Annual Review of Medicine·Stuart W PeltzAllan Jacobson
Dec 25, 2012·Nature Structural & Molecular Biology·Sebastian Pechmann, Judith Frydman
Apr 2, 2013·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Nicola AltamuraMonica Borgatti
Oct 5, 2013·Trends in Genetics : TIG·Bijoyita Roy, Allan Jacobson
Dec 18, 2013·Nature Reviews. Microbiology·Daniel N Wilson
Apr 30, 2014·Annual Review of Genomics and Human Genetics·Kim M KeelingDavid M Bedwell
Jul 16, 2014·Trends in Biochemical Sciences·Liuís Ribas de PouplanaBabak Javid
Jul 22, 2014·Cell Reports·Agnès Baudin-BaillieuOlivier Namy

❮ Previous
Next ❯

Citations

Feb 18, 2016·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Kerstin Nagel-WolfrumUwe Wolfrum
May 14, 2016·Nucleic Acids Research·Alexey RozovGulnara Yusupova
Jul 4, 2016·Trends in Biochemical Sciences·Alexey RozovGulnara Yusupova
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Bijoyita RoyAllan Jacobson
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Nadeem Siddiqui, Nahum Sonenberg
Dec 10, 2016·ACS Synthetic Biology·Purnima S KompellaSergio G Peisajovich
Aug 5, 2016·PLoS Genetics·Fabian Schueren, Sven Thoms
Mar 7, 2018·Proceedings of the National Academy of Sciences of the United States of America·Sandra BlanchetOlivier Namy
May 15, 2018·Personalized Medicine·Joanna KennyChiara Bacchelli
May 16, 2018·Nature Reviews. Molecular Cell Biology·Anthony P Schuller, Rachel Green
May 8, 2018·Cold Spring Harbor Perspectives in Biology·Christopher U T Hellen
Aug 25, 2017·Nature Microbiology·Kyle Mohler, Michael Ibba
Mar 29, 2019·PLoS Genetics·Xumin OuQiuwei Pan
Jan 9, 2020·Human Molecular Genetics·Lisha KuangHaining Zhu
Jan 25, 2020·Journal of Clinical Medicine·Monica BorgattiNicola Altamura
Sep 13, 2019·Nucleic Acids Research·Marina V RodninaFrank Peske
Jun 27, 2019·International Journal of Molecular Sciences·Dario Balestra, Alessio Branchini
Dec 19, 2019·International Journal of Molecular Sciences·Sylwia MichorowskaPiotr Wroczyński
Jul 10, 2019·International Journal of Molecular Sciences·Ambra CampofeliceIvana Pibiri
Dec 18, 2019·International Journal of Molecular Sciences·Ananya SamantaKerstin Nagel-Wolfrum
Aug 17, 2020·Molecular Biology and Evolution·Alexander T Ho, Laurence D Hurst
Oct 23, 2020·Biological Reviews of the Cambridge Philosophical Society·Martine Palma, Fabrice Lejeune
Dec 17, 2020·International Journal of Molecular Sciences·Silvia LombardiAlessio Branchini
Mar 23, 2017·Biochimica Et Biophysica Acta. General Subjects·Noah M ReynoldsAna Crnković
Jun 26, 2018·Cell Chemical Biology·Václav BeránekJason W Chin
Mar 23, 2021·Cellular and Molecular Life Sciences : CMLS·Patrícia Martins-Dias, Luísa Romão
Nov 14, 2020·International Journal of Molecular Sciences·Christine VössingJohn Neidhardt

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.