The involvement of mRNA secondary structure in protein synthesis

1987 ◽  
Vol 65 (6) ◽  
pp. 576-581 ◽  
Author(s):  
Jerry Pelletier ◽  
Nahum Sonenberg
Keyword(s):  
Secondary Structure ◽  
Translation Initiation ◽  
Binding Proteins ◽  
Atp Hydrolysis ◽  
Mrna Translation ◽  
Noncoding Region ◽  
Translational Efficiency ◽  
Mrna Secondary Structure ◽  
Complex Process ◽  
Eukaryotic Mrnas

Translation initiation in eukaryotes is a complex process involving many factors. A key step in this process is the binding of mRNA to the 43S preinitiation complex. This is generally the rate-limiting step in translation initiation and consequently a major determinant of mRNA translational efficiency. The primary and secondary structure of the mRNA 5′ noncoding region have been implicated in modulating translational efficiency. Translational efficiency was shown to be inversely proportional to the degree of secondary structure at the mRNA 5′ noncoding region. Furthermore, it was shown that cap-binding proteins that interact with the 5′ cap structure (m7GpppN) of eukaryotic mRNAs are involved in the "unwinding" of the mRNA secondary structure, in an ATP hydrolysis mediated event, to facilitate ribosome binding. Thus, cap-binding proteins can potentially regulate mRNA translation. Here, we discuss the available data supporting the notion that eukaryotic 5′ mRNA secondary structure plays an important role in translation initiation and the possible regulation of this process.

scholarly journals Making ends meet: new functions of mRNA secondary structure

2020 ◽  
Author(s):  
Dmitri N. Ermolenko ◽  
David Mathews
Keyword(s):  
Secondary Structure ◽  
Translation Initiation ◽  
Protein Complexes ◽  
Experimental Studies ◽  
Mrna Translation ◽  
Low Complexity ◽  
Mrna Secondary Structure ◽  
Protein Coding ◽  
Random Coils ◽  
Non Coding Rnas

AbstractThe 5’ cap and 3’ poly(A) tail of mRNA are known to synergistically regulate mRNA translation and stability. Recent computational and experimental studies revealed that both protein-coding and non-coding RNAs will fold with extensive intramolecular secondary structure, which will result in close distances between the sequence ends. This proximity of the ends is a sequence-independent, universal property of most RNAs. Only low-complexity sequences without guanosines are without secondary structure and exhibit end-to-end distances expected for RNA random coils. The innate proximity of RNA ends might have important biological implications that remain unexplored. In particular, the inherent compactness of mRNA might regulate translation initiation by facilitating the formation of protein complexes that bridge mRNA 5’ and 3’ ends. Additionally, the proximity of mRNA ends might mediate coupling of 3′ deadenylation to 5′ end mRNA decay.

scholarly journals Trans control of cardiac mRNA translation in a protein length-dependent fashion

2020 ◽  
Author(s):  
Franziska Witte ◽  
Jorge Ruiz-Orera ◽  
Camilla Ciolli Mattioli ◽  
Susanne Blachut ◽  
Eleonora Adami ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Translation Initiation ◽  
Phenotypic Variability ◽  
Mrna Translation ◽  
Translational Efficiency ◽  
Ribosome Assembly ◽  
List Type ◽  
Master Regulator ◽  
Protein Length ◽  
The Impact

ABSTRACTLittle is known about the impact of naturally occurring genetic variation on the rates with which proteins are synthesized by ribosomes. Here, we investigate how genetic influences on mRNA translational efficiency are associated with complex disease phenotypes using a panel of rat recombinant inbred lines. We identify a locus for cardiac hypertrophy that is associated with a translatome-wide and protein length-dependent shift in translational efficiency. This master regulator primarily affects the translation of very short and very long protein-coding sequences, altering the physiological stoichiometric translation rates of sarcomere proteins. Mechanistic dissection of this locus points to altered ribosome assembly, characterized by accumulation of polysome half-mers, changed ribosomal configurations and misregulation of the small nucleolar RNA SNORA48. We postulate that this locus enhances a pre-existing negative correlation between protein length and translation initiation in diseased hearts. Our work shows that a single genomic locus can trigger a complex, translation-driven molecular mechanism that contributes to phenotypic variability between individuals.Graphical AbstractHighlightsGenetic variability impacts protein synthesis rates in a rat model for cardiac hypertrophyA trans locus affects stoichiometric translation rates of cardiac sarcomeric proteinsThis master regulator locus induces a global, protein length-dependent shift in translationDysregulated ribosome assembly induces half-mer formation and affects translation initiation rate

scholarly journals Widespread positive selection for mRNA secondary structure at synonymous sites in domesticated yeast

2019 ◽  
Author(s):  
Minghao Yu ◽  
Wenna Guo ◽  
Qiang Wang ◽  
Jian-Qun Chen
Keyword(s):  
Secondary Structure ◽  
Positive Selection ◽  
Yeast Genome ◽  
Cellular Respiration ◽  
Translational Efficiency ◽  
Mrna Secondary Structure ◽  
Frequency Spectra ◽  
Mrna Structure ◽  
Synonymous Sites ◽  
Selection For

AbstractmRNA secondary structure assumes a critical role in gene regulation, especially for translational efficiency. Previous studies have a growing appreciation of purifying selection for the conserved mRNA structure across lineages of different species. However, the effect of mRNA structure on positive evolution remains unclear. Here, we construct a large-scale dataset of single nucleotide polymorphisms (SNPs) at synonymous sites in the population of Saccharomyces cerevisiae, combined with the experimental assessment of mRNA structure, and perform empirical population genetics data analysis through unfolded site-frequency spectra. Our results suggest that functional mRNA stem drives faster evolution of increasing GC contents itself with the purpose of regulating translational speed, which is greatly influenced by length. At the synonymous site without codon usage bias, this kind of positive selection still exists. Furthermore, mRNA secondary structure is subject to positive selection widespread among the yeast genome, particularly related to mitochondria activities, which is possibly aimed to achieve a balance between cellular respiration and alcoholic fermentation precisely at a non-protein level. It is conducive to the adaption of the dramatic environment alterations from wild to man-made environments during the domestication.

TNF-α impairs heart and skeletal muscle protein synthesis by altering translation initiation

2002 ◽  
Vol 282 (2) ◽  
pp. E336-E347 ◽  
Author(s):  
Charles H. Lang ◽  
Robert A. Frost ◽  
Angus C. Nairn ◽  
David A. MacLean ◽  
Thomas C. Vary
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Translational Efficiency ◽  
Skeletal Muscle Protein ◽  
Phosphorylation State ◽  
Tnf Α

This study examined potential mechanisms contributing to the inhibition of protein synthesis in skeletal muscle and heart after administration of tumor necrosis factor (TNF)-α. Rats had vascular catheters implanted, and TNF-α was infused continuously for 24 h. TNF-α decreased in vivo-determined rates of global protein synthesis in gastrocnemius (39%) and heart (25%). The TNF-α-induced decrease in protein synthesis in the gastrocnemius involved a reduction in the synthesis of both myofibrillar and sarcoplasmic proteins. To identify potential mechanisms responsible for regulating mRNA translation, we examined several eukaryotic initiation factors (eIFs) and elongation factors (eEFs). TNF-α decreased the activity of eIF-2B in muscle (39%) but not in heart. This diminished activity was not caused by a reduction in the content of eIF-2Bε or the content and phosphorylation state of eIF-2α. Skeletal muscle and heart from TNF-α-treated rats demonstrated 1) an increased binding of the translation repressor 4E-binding protein-1 (4E-BP1) with eIF-4E, 2) a decreased amount of eIF-4E associated with eIF-4G, and 3) a decreased content of the hyperphosphorylated γ-form of 4E-BP1. In contrast, the infusion of TNF-α did not alter the content of eEF-1α or eEF-2, or the phosphorylation state of eEF-2. In summary, these data suggest that TNF-α impairs skeletal muscle and heart protein synthesis, at least in part, by decreasing mRNA translational efficiency resulting from an impairment in translation initiation associated with alterations in eIF-4E availability.

scholarly journals Light-Dependent Translation Change of Arabidopsis psbA Correlates with RNA Structure Alterations at the Translation Initiation Region

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 322
Author(s):  
Piotr Gawroński ◽  
Christel Enroth ◽  
Peter Kindgren ◽  
Sebastian Marquardt ◽  
Stanisław Karpiński ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Translation Initiation ◽  
Rna Structure ◽  
Regulatory Protein ◽  
High Light ◽  
Ribosome Profiling ◽  
General Mechanism ◽  
Mrna Secondary Structure ◽  
Translation Initiation Region

mRNA secondary structure influences translation. Proteins that modulate the mRNA secondary structure around the translation initiation region may regulate translation in plastids. To test this hypothesis, we exposed Arabidopsis thaliana to high light, which induces translation of psbA mRNA encoding the D1 subunit of photosystem II. We assayed translation by ribosome profiling and applied two complementary methods to analyze in vivo RNA secondary structure: DMS-MaPseq and SHAPE-seq. We detected increased accessibility of the translation initiation region of psbA after high light treatment, likely contributing to the observed increase in translation by facilitating translation initiation. Furthermore, we identified the footprint of a putative regulatory protein in the 5′ UTR of psbA at a position where occlusion of the nucleotide sequence would cause the structure of the translation initiation region to open up, thereby facilitating ribosome access. Moreover, we show that other plastid genes with weak Shine-Dalgarno sequences (SD) are likely to exhibit psbA-like regulation, while those with strong SDs do not. This supports the idea that changes in mRNA secondary structure might represent a general mechanism for translational regulation of psbA and other plastid genes.

scholarly journals Predicting in vivo binding sites of RNA-binding proteins using mRNA secondary structure

RNA ◽  
2010 ◽  
Vol 16 (6) ◽  
pp. 1096-1107 ◽  
Author(s):  
X. Li ◽  
G. Quon ◽  
H. D. Lipshitz ◽  
Q. Morris
Keyword(s):  
Secondary Structure ◽  
Binding Sites ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Secondary Structure ◽  
In Vivo Binding

scholarly journals Recognition of Yeast mRNAs as “Nonsense Containing” Leads to Both Inhibition of mRNA Translation and mRNA Degradation: Implications for the Control of mRNA Decapping

1999 ◽  
Vol 10 (11) ◽  
pp. 3971-3978 ◽  
Author(s):  
Denise Muhlrad ◽  
Roy Parker
Keyword(s):  
Premature Termination ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Mrna Translation ◽  
Premature Termination Codon ◽  
Mrna Degradation ◽  
Translational Efficiency ◽  
Mrna Decapping ◽  
The Status ◽  
Eukaryotic Mrnas

A critical step in the degradation of many eukaryotic mRNAs is a decapping reaction that exposes the transcript to 5′ to 3′ exonucleolytic degradation. The dual role of the cap structure as a target of mRNA degradation and as the site of assembly of translation initiation factors has led to the hypothesis that the rate of decapping would be specified by the status of the cap binding complex. This model makes the prediction that signals that promote mRNA decapping should also alter translation. To test this hypothesis, we examined the decapping triggered by premature termination codons to determine whether there is a down-regulation of translation when mRNAs were recognized as “nonsense containing.” We constructed an mRNA containing a premature stop codon in which we could measure the levels of both the mRNA and the polypeptide encoded upstream of the premature stop codon. Using this system, we analyzed the effects of premature stop codons on the levels of protein being produced per mRNA. In addition, by using alterations either in cis or intrans that inactivate different steps in the recognition and degradation of nonsense-containing mRNAs, we demonstrated that the recognition of a nonsense codon led to a decrease in the translational efficiency of the mRNA. These observations argue that the signal from a premature termination codon impinges on the translation machinery and suggest that decapping is a consequence of the change in translational status of the mRNA.

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