Previous experiments have shown that limitation for certain aminoacyl-tRNA species results in phenotypic suppression of a subset of frameshift mutant alleles, including members in both the (+) and (-) incorrect reading frames. Here, we demonstrate that such phenotypic suppression can occur through a ribosome reading frame shift at a hungry AAG codon calling for lysyl-tRNA in short supply. Direct amino acid sequence analysis of the product and DNA sequence manipulation of the gene demonstrate that the ribosome frameshift occurs through a movement of one base to the left, so as to decode the triplet overlapping the hungry codon from the left or 5' side, followed by continued normal translation in the new, shifted reading frame.
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http://dx.doi.org/10.1016/0022-2836(92)90713-t | DOI Listing |
Pediatr Endocrinol Diabetes Metab
September 2023
Cardiology, Vardhman Mahavir Medical College and Safdarjung Hospital, India.
Biol Chem
July 2023
Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, D-37077 Göttingen, Germany.
In each round of translation elongation, the ribosome translocates along the mRNA by precisely one codon. Translocation is promoted by elongation factor G (EF-G) in bacteria (eEF2 in eukaryotes) and entails a number of precisely-timed large-scale structural rearrangements. As a rule, the movements of the ribosome, tRNAs, mRNA and EF-G are orchestrated to maintain the exact codon-wise step size.
View Article and Find Full Text PDFTrends Genet
November 2022
Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands; Erasmus MC, Rotterdam University, Rotterdam, The Netherlands. Electronic address:
Programmed ribosomal frameshifting (PRF) is a key mechanism that viruses use to generate essential proteins for replication, and as a means of regulating gene expression. PRF generally involves recoding signals or frameshift stimulators to elevate the occurrence of frameshifting at shift-prone 'slippery' sequences. Given its essential role in viral replication, targeting PRF was envisioned as an attractive tool to block viral infection.
View Article and Find Full Text PDFInt J Mol Sci
December 2018
Institute of Biochemistry, National Chung-Hsing University, 145 Xingda Road, Taichung 402, Taiwan.
In contrast to -1 programmed ribosomal frameshifting (PRF) stimulation by an RNA pseudoknot downstream of frameshifting sites, a refolding upstream RNA hairpin juxtaposing the frameshifting sites attenuates -1 PRF in human cells and stimulates +1 frameshifting in yeast. This eukaryotic functional mimicry of the internal Shine-Dalgarno (SD) sequence-mediated duplex was confirmed directly in the 70S translation system, indicating that both frameshifting regulation activities of upstream hairpin are conserved between 70S and 80S ribosomes. Unexpectedly, a downstream pseudoknot also possessed two opposing hungry codon-mediated frameshifting regulation activities: attenuation of +1 frameshifting and stimulation of a non-canonical -1 frameshifting within the +1 frameshift-prone CUUUGA frameshifting site in the absence of release factor 2 (RF2) in vitro.
View Article and Find Full Text PDFRNA
October 2018
School of Biochemistry and Cell Biology, Western Gateway Building, University College Cork, Cork, Ireland.
The process of translation is characterized by irregularities in the local decoding rates of specific mRNA codons. This includes the occurrences of long pauses that can take place when ribosomes decode certain peptide sequences, encounter strong RNA secondary structures, or decode "hungry" codons. Examples are known where such pausing or stalling is used for regulating protein synthesis.
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