Attenuation in the control of expression of bacterial operons

Yanofsky, Charles

doi:10.1038/289751a0

Cited by 733 publications

(444 citation statements)

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“…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). Indeed, it has been postulated that ribosomal pausing may be involved in the decay of other mRNAs (6,13).…”

Section: Discussionmentioning

confidence: 99%

“…There are numerous possible mechanisms by which a putative ribosomal pause could stimulate mRNA turnover mediated by the MIE. For instance, a ribosome stalled at a particular site might affect RNA folding (43) and promote formation of a structure that is recognized as a signal for decay. Alternatively, a pause in translational elongation might permit sequences 3' of the pause to be relatively ribosome free.…”

Section: Discussionmentioning

confidence: 99%

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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%

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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“…However, this inhibition is ''leaky'': there is some transcription of the operon even in the presence of tryptophan; this would waste energy for producing enzymes that are not needed. A second regulatory mechanism, called attenuation, knocks down this residual transcription on the trp operon [2,3].…”

Section: The Experimentsmentioning

confidence: 99%

Problem‐solving test: Attenuation: A mechanism to regulate bacterial tryptophan biosynthesis

Szeberényi

2010

Biochem Molecular Bio Educ

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Terms to be familiar with before you start to solve the test: tryptophan, transcription unit, operon, trp repressor, corepressor, operator, promoter, palindrome, initiation, elongation, and termination of transcription, open reading frame, coupled transcription/translation, chromosome-polysome complex.Keywords: gene expression, metabolic pathways and regulation, problem-based learning. THE EXPERIMENTAs presented in the problem-solving test in the last issue of Biochemistry and Molecular Biology Education [1], the transcription unit encoding the enzymes of tryptophan biosynthesis is regulated by the trp 1 repressor: tryptophan acting as a corepressor binds to and activates the repressor, which in turn binds to the operator region and blocks the movement of RNA polymerase and, thus, the transcription of the structural genes trp E, D, C, B, and A coding for enzymes of tryptophan synthesis. However, this inhibition is ''leaky'': there is some transcription of the operon even in the presence of tryptophan; this would waste energy for producing enzymes that are not needed. A second regulatory mechanism, called attenuation, knocks down this residual transcription on the trp operon [2,3].A short region between the operator and the first structural gene (trp E), called leader ( Fig. 1), is responsible for attenuation. The leader sequence is 140 basepairs long and codes for the 5 0 -end region of trp mRNA preceding the initiation codon of the first structural gene. The leader region of trp mRNA has a unique structure (Fig. 2a). It contains a short open reading frame (ORF) coding for an oligopeptide called leader peptide. Two palindromic sequences (region 1/2 and region 3/4) produce self-complementary basepairing that leads to the formation of hairpin structures. The second hairpin (region 3/4) is followed by a stretch of Us, creating a structural characteristic of certain transcription terminators. The ORF coding for the leader peptide overlaps with region 1 and contains two codons for tryptophan. In addition, regions 2 and 3 are complementary not only to regions 1 and 4, respectively, but to each other as well. This rather complicated structure of the leader sequence sets the stage for an ingenious mechanism of regulation for the transcription of the operon.Attenuation is based on coupled transcription/translation in prokaryotes: ribosomes bind to nascent mRNAs forming chromosome-polysome complexes; thus, protein synthesis starts on growing mRNA chains. If tryptophan is not available (Fig. 2b), the ribosome stalls in the leader peptide coding ORFs disrupting hairpin 1/2 and leading to the formation of hairpin 2/3. This hairpin prevents the generation of the termination hairpin 3/4 (called attenuator), and, thus, RNA polymerase is able to continue elongation and transcribes the whole operon into a full-length transcript. However, if tryptophan is present, the ribosome keeps moving and prevents the formation of both hairpin 1/2 and 2/3 (Fig. 2c). The attenuator hairpin 3/4 can form and terminates transcription. The leader ...

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“…17 The leader transcript refers to the 162 nt long untranslated region (UTR) preceding the structural genes. 10 Along this leader transcript, the ribosomal binding site resides at the 5' end, 18 and an internal transcription termination signal is located distally before the first structural gene E. 10,19 This termination signal, lying within the attenuator, can be recognised by RNA polymerase to produce a transcript of about 140 nt (137-141) length. 9.20 This shorter transcript generates a leader peptide consisting of 14 residues whose distal end has a tandem of trp residues.…”

Section: Trp Operon Leadermentioning

confidence: 99%

“…9.20 This shorter transcript generates a leader peptide consisting of 14 residues whose distal end has a tandem of trp residues. 10 This leader peptide is involved in the attenuation regulatory strategy where the Trp operon leader is utilised for adaptation to the metabolic condition concerning the biosynthesis of trp. 9 Attenuation in Tryptophan operon leader The trp-activated repressor protein (trpR) is stimulated upon trp binding to compete against RNA polymerase, 21 and consequently switches off the initiation of trp operon transcription.…”

Section: Trp Operon Leadermentioning

confidence: 99%

Four RNA families with functional transient structures

Zhu

Meyer

2015

RNA Biology

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P rotein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since RFAM annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing RFAM families or introduce a new RNA family to RFAM. For each of the four RNA families, we compile a multiplesequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5 0 flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5 0 UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All transient and dominant structures are mapped to our new alignments introduced here.

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Attenuation in the control of expression of bacterial operons

Cited by 733 publications

References 74 publications

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

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

Problem‐solving test: Attenuation: A mechanism to regulate bacterial tryptophan biosynthesis

Four RNA families with functional transient structures

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