Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site

Belcourt, Michael F.; Farabaugh, Philip J.

doi:10.1016/0092-8674(90)90371-k

Cited by 290 publications

(298 citation statements)

References 58 publications

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“…The observation that rare codons are a component of the MIE suggests a means through which translation and decay of the AL4ToLl mRNA may be coupled. It has been shown that in some cases rare codons can slow elongation rates along an mRNA and cause ribosomal pausing (4,8,33,38,42). Moreover, nonuniform translation rates along individual mRNAs have been implicated as being important in a number of cellular processes, including protein secretion, frameshifting, transcriptional attenuation, and protein folding (2,4,11,39,43).…”

Section: Discussionmentioning

confidence: 99%

A small segment of the MAT alpha 1 transcript promotes mRNA decay in Saccharomyces cerevisiae: a stimulatory role for rare codons.

1993

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Differences in decay rates of eukaryotic transcripts can be determined by discrete sequence elements within mRNAs. Through the analysis of chimeric transcripts and internal deletions, we have identified a 65-nucleotide segment of the AL4Tal mRNA coding region, termed the AL4TaJ instability element, that is sufficient to confer instability to a stable PGKI reporter transcript and that accelerates turnover of the unstable AL4TaI mRNA.This 65-nucleotide element is composed of two parts, one located within the 5' 33 nucleotides and the second located in the 3' 32 nucleotides. The first part, which can be functionally replaced by sequences containing rare codons, is unable to promote rapid decay by itself but can enhance the action of the 3' 32 nucleotides (positions 234 to 266 in the AL4Tal mRNA) in accelerating turnover. A second portion of the MA4Ta) mRNA (nucleotides 265 to 290) is also sufficient to destabilize the PGKI reporter transcript when positioned 3' of rare codons, suggesting that the 3' half of the MATal instability element is functionally reiterated within the MA4TcJ mRNA. The observation that rare codons are part of the 65-nucleotide MAToJ instability element suggests possible mechanisms through which translation and mRNA decay may be linked.The regulation of eukaryotic gene expression can be significantly affected by differences in mRNA decay rates. Critical to the understanding of mRNA turnover is a detailed knowledge of the mRNA features that specify differences in decay rates. Recent experiments, examining the decay rates of chimeric and/or mutant transcripts, suggest that at least in some cases, there are discrete sequence elements that affect mRNA turnover rates (for reviews, see references 19 and 28). These instability elements have been described in the protein coding and/or 3' untranslated regions of a small number of mRNAs.Determinants of mRNA stability have been identified in the protein coding regions of mammalian (14,32,41) and yeast (16,17,27,36) transcripts. These observations suggest that the coding region will be a common location for sequences that affect mRNA half-lives (t1j2s). However, the critical features of such coding-region stability determinants, and how these elements function in the presence of translocating ribosomes, are largely unknown. Recent results suggest that recognition of information in the coding region specifying mRNA decay rates may occur by two distinctly different mechanisms. In the case of the mammalian 3-tubulin mRNA, recognition occurs at the level of the nascent peptide, demonstrating how translation and decay can be linked (44). Alternatively, coding-region determinants in c-fos and c-myc mRNAs may be recognized by proteins that bind directly to the RNA (6, 10), although the relationship between protein binding, mRNA decay, and translocating ribosomes is unclear.The genetic approaches possible in the yeast Saccharomyces cerevisiae make this organism a useful system for the analysis of eukaryotic mRNA decay. Previously, we reported that a 363-nucleotide...

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Section: Discussionmentioning

confidence: 99%

A small segment of the MAT alpha 1 transcript promotes mRNA decay in Saccharomyces cerevisiae: a stimulatory role for rare codons.

1993

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“…the retroviral gag and pol genes (Farabaugh et al, 1993); e.g. the retrotransposon TYA and TYB genes (Belcourt and Farabaugh, 1990); (ii) regulating gene expression, e.g. the Escherichia coli prfB gene (e.g.…”

Section: Biological Consequences Which Could Be Associated With the Pmentioning

confidence: 99%

A code in the protein coding genes

Arquès

Michel

1997

Biosystems

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A statistical analysis with 12 288 autocorrelation functions applied in protein (coding) genes of prokaryotes and eukaryotes identifies three subsets of trinucleotides in their three frames: T 0 = X 0 @ {AAA, TTT} with X 0 = {AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} in frame 0 (the reading frame established by the ATG start trinucleotide), T 1 = X 1 @ {CCC} in frame 1 and T 2 = X 2 @{GGG} in frame 2 (the frames 1 and 2 being the frame 0 shifted by one and two nucleotides, respectively, to the right). These three subsets are identical in these two gene populations and have five important properties: (i) the property of maximal (20 trinucleotides) circular code for X 0 (resp. X 1 , X 2 ) allowing to retrieve automatically the frame 0 (resp. 1, 2) in any region of the gene without start codon; (ii) the DNA complementarity property C (e.g. C(AAC)= GTT): C(T 0 )=T 0 , C(T 1 )=T 2 and C(T 2 )=T 1 allowing the two paired reading frames of a DNA double helix simultaneously to code for amino acids; (iii) the circular permutation property P (e.g. P(AAC)= ACA): P(X 0 )=X 1 and P(X 1 )=X 2 implying that the two subsets X 1 and X 2 can be deduced from X 0 ; (iv) the rarity property with an occurrence probability of X 0 =6×10 − 8 ; and (v) the concatenation properties in favour of an evolutionary code: a high frequency (27.5%) of misplaced trinucleotides in the shifted frames, a maximum (13 nucleotides) length of the minimal window to retrieve automatically the frame and an occurrence of the four types of nucleotides in the three trinucleotide sites. In Discussion, a simulation based on an independent mixing of the trinucleotides of T 0 allows to retrieve the two subsets T 1 and T 2 . Then, the identified subsets T 0 , T 1 and T 2 replaced in the 2-letter genetic alphabet {R, Y} (R =purine= A or G, Y=pyrimidine= C or T) allow to retrieve the RNY model (N=R or Y) and to explain previous works in the alphabet {R, Y}. Then, these three subsets are related to the genetic code. The trinucleotides of T 0 code for 13 amino acids: Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Thr, Tyr and Val. Finally, a strong correlation between the usage of the trinucleotides of T 0 in protein genes and the amino acid frequencies in proteins is observed as six among seven amino acids not coded by T 0 , have as expected the lowest frequencies in proteins of both prokaryotes and eukaryotes.

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“…3,4 While Gag can be readily translated as an immature Gag-p49 form, Pol synthesis requires a ribosomal frameshift, creating a template for the production of a Gag-Pol fusion protein that is further processed by proteolysis. 5,6 Similar to retroviruses, Ty1 genomic RNA, Gag and unprocessed Gag-Pol assemble to form immature VLPs. 7 VLP maturation, including the proteolytic conversion of Gag-p49 into Gag-p45 and the precise cleavage of GagPol, both achieved by a protease function contained in Pol, is a prerequisite for Ty1 RNA reverse transcription and transposition.…”

Section: Introductionmentioning

confidence: 99%