scholarly journals Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation

2019 ◽  
Vol 47 (5) ◽  
pp. 2216-2228 ◽  
Author(s):  
Rodolfo L Carneiro ◽  
Rodrigo D Requião ◽  
Silvana Rossetto ◽  
Tatiana Domitrovic ◽  
Fernando L Palhano
2018 ◽  
Author(s):  
Rodolofo L. Carneiro ◽  
Rodrigo D. Requião ◽  
Silvana Rossetto ◽  
Tatiana Domitrovic ◽  
Fernando L. Palhano

SummaryDifferent methods of mRNA half-life measurements are available, but genome-wide measurements of mRNA half-life in yeast showed a weak correlation between the methods. Moreover, when we compared mRNA half-life determined by these methods with other cellular measurements such as mRNA and protein abundance low correlation was found. To clarify this matter, we analyzed mRNA half-life datasets from nine different groups to determine the most accurate method of measurement. Since codon optimality is one of the significant determinants of mRNA stability, we used the codon stabilization coefficient (CSC) as a reference for mRNA half-life measurement accuracy. After CSC calculation for each dataset, we find strong positive correlations between the CSC from some datasets with other parameters that reflect codon optimality such as tRNA abundance and ribosome residence time. By the use of CSC parameter, we observed that most genes contain non-optimal codons and that codon bias exists toward optimized and non-optimized genes. We also observed that stretches of non-optimal are not randomly distributed since it causes impacts on translation.


2019 ◽  
Author(s):  
Fabian Hia ◽  
Sheng Fan Yang ◽  
Yuichi Shichino ◽  
Masanori Yoshinaga ◽  
Yasuhiro Murakawa ◽  
...  

AbstractCodon bias has been implicated as one of the major factors contributing to mRNA stability in yeast. However, the effects of codon-bias on mRNA stability remain unclear in humans. Here we show that human cells possess a mechanism to modulate RNA stability through a unique codon bias different from that of yeast. Bioinformatics analysis showed that codons could be clustered into two distinct groups – codons with G or C at the third base position (GC3) and codons with either A or T at the third base position (AT3); the former stabilizing while the latter destabilizing mRNA. Quantification of codon bias showed that increased GC3 content entails proportionately higher GC content. Through bioinformatics, ribosome profiling andin vitroanalysis, we show that decoupling of the effects of codon bias reveals two modes of mRNA regulation, GC3- and GC-content dependent. Employing an immunoprecipitation-based strategy, we identified ILF2 as an RNA binding protein that differentially regulates global mRNA abundances based on codon bias. Our results demonstrate that codon bias is a two-pronged system that governs mRNA abundance.


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