scholarly journals Hallmarks of slow translation initiation revealed in mitochondrially localizing mRNA sequences

2019 ◽  
Author(s):  
Thomas M. Poulsen ◽  
Kenichiro Imai ◽  
Martin C. Frith ◽  
Paul Horton
Keyword(s):  
Translation Initiation ◽  
Experimental Studies ◽  
Mrna Translation ◽  
Mitochondrial Localization ◽  
Initiation Rate ◽  
Mrna Binding Protein ◽  
Mrna Length ◽  
Mrna Binding ◽  
Reduced Mobility ◽  
The Relationship

ABSTRACTThe mRNA of some, but not all, nuclear encoded mitochondrial proteins localize to the periphery of mitochondria. Previous studies have shown that both the nascent polypeptide chain and an mRNA binding protein play a role in this phenomenon, and have noted a positive correlation between mRNA length and mitochondrial localization. Here, we report the first investigation into the relationship between mRNA translation initiation rate and mRNA mitochondrial localization. Our results indicate that translation initiation promoting factors such as Kozak sequences are associated with cytosolic localization, while inhibiting factors such as 5′ UTR secondary structure correlate with mitochondrial localization. Moreover, the frequencies of nucleotides in various positions of the 5′ UTR show higher correlation with localization than the 3′ UTR. These results indicate that mitochondrial localization is associated with slow translation initiation. Interestingly this may help explain why short mRNAs, which are thought to initiate translation rapidly, seldom localize to mitochondria. We propose a model in which translating mRNA has reduced mobility and tends not to reach mitochondria. Finally, we explore this model with a simulation of mRNA diffusion using previously estimated translation initiation probabilities, confirming that our model can produce localization values similar to those measured in experimental studies.

scholarly journals Circular RNA, the Key for Translation

2020 ◽  
Vol 21 (22) ◽  
pp. 8591
Author(s):  
Anne-Catherine Prats ◽  
Florian David ◽  
Leila H. Diallo ◽  
Emilie Roussel ◽  
Florence Tatin ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translational Control ◽  
Mrna Translation ◽  
Circular Rna ◽  
Initiation Factor ◽  
Circular Rnas ◽  
Strong Impact ◽  
Initiation Rate ◽  
New Family ◽  
Independent Translation

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m6A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5′ end-independent translation initiation. Today a new family of so-called “noncoding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5′ end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3′–5′ interaction have been reported, including m6A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and noncovalently closed circular mRNA translation landscape shows that RNA with circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

scholarly journals Extrinsic noise acts to lower protein production at higher translation initiation rates

2020 ◽  
Author(s):  
Rati Sharma
Keyword(s):  
Translation Initiation ◽  
Protein Production ◽  
Translation Termination ◽  
Mrna Translation ◽  
Intrinsic Noise ◽  
Stochastic Simulations ◽  
Residence Times ◽  
Extrinsic Noise ◽  
Initiation Rate ◽  
The Individual

Any cellular process at the microscopic level is governed by both extrinsic and intrinsic noise. In this article, we incorporate extrinsic noise in a model of mRNA translation and carry out stochastic simulations of the same. We then evaluate various statistics related to the residence time of the ribosome on the mRNA and subsequent protein production. We also study the effect of slow codons. From our simulations, we show that noise in the translation initiation rate rather than the translation termination rate acts to significantly broaden the distribution of mRNA residence times near the membrane. Further, the presence of slow codons acts to increase the mean residence times. However, this increase also depends on the number and position of the slow codons on the lattice. We also show that the the slow codons act to mask any effect from the extrinsic noise themselves. Our results have implications towards a better understanding of the role the individual components play during the translation 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 A repeated IMP-binding motif controls oskar mRNA translation and anchoring independently of Drosophila melanogaster IMP

2006 ◽  
Vol 172 (4) ◽  
pp. 577-588 ◽  
Author(s):  
Trent P. Munro ◽  
Sunjong Kwon ◽  
Bruce J. Schnapp ◽  
Daniel St Johnston
Keyword(s):  
Drosophila Melanogaster ◽  
Rna Binding ◽  
Binding Protein ◽  
Mrna Translation ◽  
Binding Motif ◽  
Insulin Growth Factor ◽  
Factor Ii ◽  
Mrna Binding Protein ◽  
Exponential Enrichment ◽  
Mrna Binding

Zip code–binding protein 1 (ZBP-1) and its Xenopus laevis homologue, Vg1 RNA and endoplasmic reticulum–associated protein (VERA)/Vg1 RNA-binding protein (RBP), bind repeated motifs in the 3′ untranslated regions (UTRs) of localized mRNAs. Although these motifs are required for RNA localization, the necessity of ZBP-1/VERA remains unresolved. We address the role of ZBP-1/VERA through analysis of the Drosophila melanogaster homologue insulin growth factor II mRNA–binding protein (IMP). Using systematic evolution of ligands by exponential enrichment, we identified the IMP-binding element (IBE) UUUAY, a motif that occurs 13 times in the oskar 3′UTR. IMP colocalizes with oskar mRNA at the oocyte posterior, and this depends on the IBEs. Furthermore, mutation of all, or subsets of, the IBEs prevents oskar mRNA translation and anchoring at the posterior. However, oocytes lacking IMP localize and translate oskar mRNA normally, illustrating that one cannot necessarily infer the function of an RBP from mutations in its binding sites. Thus, the translational activation of oskar mRNA must depend on the binding of another factor to the IBEs, and IMP may serve a different purpose, such as masking IBEs in RNAs where they occur by chance. Our findings establish a parallel requirement for IBEs in the regulation of localized maternal mRNAs in D. melanogaster and X. laevis.

scholarly journals Circular RNA, the Key for Translation

2020 ◽  
Author(s):  
Anne-Catherine Prats ◽  
Florian David ◽  
Leila Diallo ◽  
Emilie Roussel ◽  
Florence Tatin ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translational Control ◽  
Mrna Translation ◽  
Circular Rna ◽  
Initiation Factor ◽  
Circular Rnas ◽  
Strong Impact ◽  
Initiation Rate ◽  
New Family ◽  
Independent Translation

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m6A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m6A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

scholarly journals Circular RNA, the Key for Translation

2020 ◽  
Author(s):  
Anne-Catherine Prats ◽  
Florian David ◽  
Leila Diallo ◽  
Emilie Roussel ◽  
Florence Tatin ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translational Control ◽  
Mrna Translation ◽  
Circular Rna ◽  
Initiation Factor ◽  
Circular Rnas ◽  
Strong Impact ◽  
Initiation Rate ◽  
New Family ◽  
Independent Translation

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m6A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of non-coding RNAs, circular RNAs (circRNAs), has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m6A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape is the rule for translation with an important impact on disease development.

Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure

2018 ◽  
Vol 24 (3) ◽  
pp. 341-358 ◽  
Author(s):  
Xiaotong Ji ◽  
Yingying Zhang ◽  
Guangke Li ◽  
Nan Sang
Keyword(s):  
Heart Failure ◽  
Particulate Matter ◽  
Inflammatory Response ◽  
Heart Diseases ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Inflammatory Mechanism ◽  
High Concentrations ◽  
Future Work ◽  
The Relationship

Recently, numerous studies have found that particulate matter (PM) exposure is correlated with increased hospitalization and mortality from heart failure (HF). In addition to problems with circulation, HF patients often display high expression of cytokines in the failing heart. Thus, as a recurring heart problem, HF is thought to be a disorder characterized in part by the inflammatory response. In this review, we intend to discuss the relationship between PM exposure and HF that is based on inflammatory mechanism and to provide a comprehensive, updated evaluation of the related studies. Epidemiological studies on PM-induced heart diseases are focused on high concentrations of PM, high pollutant load exposure in winter, or susceptible groups with heart diseases, etc. Furthermore, it appears that the relationship between fine or ultrafine PM and HF is stronger than that between HF and coarse PM. However, fewer studies paid attention to PM components. As for experimental studies, it is worth noting that coarse PM may indirectly promote the inflammatory response in the heart through systematic circulation of cytokines produced primarily in the lungs, while ultrafine PM and its components can enter circulation and further induce inflammation directly in the heart. In terms of PM exposure and enhanced inflammation during the pathogenesis of HF, this article reviews the following mechanisms: hemodynamics, oxidative stress, Toll-like receptors (TLRs) and epigenetic regulation. However, many problems are still unsolved, and future work will be needed to clarify the complex biologic mechanisms and to identify the specific components of PM responsible for adverse effects on heart health.

scholarly journals Experimental studies on the transformation from firn to ice in the wet-snow zone of temperate glaciers

1997 ◽  
Vol 24 ◽  
pp. 181-185 ◽  
Author(s):  
Katsuhisa Kawashima ◽  
Tomomi Yamada
Keyword(s):  
Experimental Studies ◽  
Ice Formation ◽  
Compression Tests ◽  
Densification Rate ◽  
Overburden Pressure ◽  
Proportionality Constant ◽  
Wet Snow ◽  
Water Saturated ◽  
The Relationship ◽  
Good Agreement

The densification of water-saturated firn, which had formed just above the firn-ice transition in the wet-snow zone of temperate glaciers, was investigated by compression tests under pressures ranging from 0.036 to 0.173 MPa, with special reference to the relationship between densification rate, time and pressure. At each test, the logarithm of the densification rate was proportional to the logarithm of the time, and its proportionality constant increased exponentially with increasing pressure. The time necessary for ice formation in the firn aquifer was calculated using the empirical formula obtained from the tests. Consequently, the necessary time decreased exponentially as the pressure increased, which shows that the transformation from firn in ice can be completed within the period when the firn aquifer exists, if the overburden pressure acting on the water-saturated firn is above 0.12–0.14 MPa. This critical value of pressure was in good agreement with the overburden pressure obtained from depth–density curves of temperate glaciers. It was concluded that the depth of firn–ice transition was self-balanced by the overburden pressure to result in the concentration between 20 and 30 m.

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