Universally increased mRNA stability downstream of the translation initiation site in eukaryotes and prokaryotes

Mao, Yuanhui; Wang, Wangtian; Cheng, Nan; Li, Qian; Tao, Shiheng

doi:10.1016/j.gene.2012.12.062

Cited by 8 publications

(12 citation statements)

References 49 publications

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“…Third, we show that the "transition peak," a region of selection for strong mRNA folding beginning around 30-70 nt downstream of the start codon that was reported elsewhere to be associated with translation efficiency [18,35,36,45], appears frequently (45%) in the analyzed organisms, indicating this mechanism is common ( Fig. 1a, c).…”

Section: Discussionsupporting

confidence: 65%

“…1a, region B). It was suggested ( [34,35], based solely on evidence in Eschericia coli and Saccharomyces cerevisiae) that this peak is responsible for increasing translation throughput, by minimizing ribosomal traffic jams occurring because of uneven translation elongation rates throughout the CDS. There is also some evidence [4,9] that strong secondary structure downstream of the start codon can enhance translation.…”

Section: Conserved Regions Of Folding Bias (δLfe)mentioning

confidence: 99%

“…Studies focusing on the beginning of the coding region (i.e., the first 40-50 nucleotides) found evidence for the inverse, with selection acting to weaken mRNA folding in that region [30,[32][33][34]. In addition, there is some evidence for specifically strong folding in nucleotides 30-70, which may slow down translation elongation near the 5′ end of the mRNA, possibly to prevent ribosomal traffic jams [18,35,36]. Finally, it has been suggested that folding is weakened in the region leading to the stop codon [32][33][34], but not in a way that attributes this weakening to direct selection on folding strength rather than a side effect of some other bias in this region.…”

Section: Introductionmentioning

confidence: 99%

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High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life

Peeri

Tuller

2020

Genome Biol

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Background: mRNA can form local secondary structure within the protein-coding sequence, and the strength of this structure is thought to influence gene expression regulation. Previous studies suggest that secondary structure strength may be maintained under selection, but the details of this phenomenon are not well understood. Results: We perform a comprehensive study of the selection on local mRNA folding strengths considering variation between species across the tree of life. We show for the first time that local folding strength selection tends to follow a conserved characteristic profile in most phyla, with selection for weak folding at the two ends of the coding region and for strong folding elsewhere in the coding sequence, with an additional peak of selection for strong folding located downstream of the start codon. The strength of this pattern varies between species and organism groups, and we highlight contradicting cases. To better understand the underlying evolutionary process, we show that selection strengths in the different regions are strongly correlated, and report four factors which have a clear predictive effect on local mRNA folding selection within the coding sequence in different species. Conclusions: The correlations observed between selection for local secondary structure strength in the different regions and with the four genomic and environmental factors suggest that they are shaped by the same evolutionary process throughout the coding sequence, and might be maintained under direct selection related to optimization of gene expression and specifically translation regulation.

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Section: Discussionsupporting

confidence: 65%

Section: Conserved Regions Of Folding Bias (δLfe)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life

Peeri

Tuller

2020

Genome Biol

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“…In some cases it apparently does not increase gene expression at all and in other cases up to 1000-fold [1 ,3 ,4,5]. It is also debated how codon usage effects other features of the underlying transcript like for example RNA folding, that might result in changes of protein expression level [6].…”

Section: Introductionmentioning

confidence: 99%

“…However, there are several other factors that influence the choice of codons at certain positions like maintaining mRNA structure [18] or tissue specific expression [19,20]. Akin to [6], previous work could link mRNA stability with the first nucleotides of the coding sequence and further with tRNA abundance and ribosome density during translation [21]. Altering the structure of mRNA can also be used to introduce synthetic riboswitches to induce or repress gene expression via external triggers as reviewed in [22].…”

Section: Introductionmentioning

confidence: 99%

Means to optimize protein expression in transgenic plants

Ullrich

Hiß

Rensing

2015

Current Opinion in Biotechnology

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Deciphering the Rules of Ribosome Binding Site Differentiation in Context Dependence

et al. 2022

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The ribosome binding site (RBS) is a crucial element regulating translation. However, the activity of RBS is poorly predictable, because it is strongly affected by the local possible secondary structure, that is, context dependence. By the Flowseq technique, over 20 000 RBS variants were sorted and sequenced, and the translation of multiple genes under the same RBS was quantitatively characterized to evaluate the context dependence of each RBS variant in E. coli. Two regions, (−7 to −2) and (−17 to −12), of RBS were predicted with a higher possibility to pair with each other to slow down the translation initiation. Associations between phenotypes and the intrinsic factors suspected to affect translation efficiency and context dependence of the RBS, including nucleotide bias at each position, free energy, and conservation, were disentangled. The results showed that translation efficiency was influenced more significantly by conservation of the SD region (−16 to −8), while an AC-rich spacer region (−7 to −1) was associated with low context dependence. We confirmed these characteristics using a series of synthesized RBSs. The average correlation between multiple reporters was significantly higher for RBSs with an AC-rich spacer (0.714) compared with a GU-rich spacer (0.286). Overall, we proposed general design criteria to improve programmability and minimize context dependence of RBS. The characteristics unraveled here can be adapted to other bacteria for fine-tuning target-gene expression.

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Universally increased mRNA stability downstream of the translation initiation site in eukaryotes and prokaryotes

Cited by 8 publications

References 49 publications

High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life

High-resolution modeling of the selection on local mRNA folding strength in coding sequences across the tree of life

Means to optimize protein expression in transgenic plants

Deciphering the Rules of Ribosome Binding Site Differentiation in Context Dependence

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