Codon usage and splicing jointly influence mRNA localization

Mordstein, Christine

doi:10.26226/morressier.5ebd45acffea6f735881af45

Cited by 3 publications

(1 citation statement)

References 57 publications

(69 reference statements)

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“…Corroborating these studies, a recent study by Mordstein and colleagues demonstrated that through genomewide analysis and optimization of codons, high GC-content increased mRNA and protein abundance, as well as cytoplasmic localization [160]. Interestingly however, the authors also showed that splicing increases the expression of AT-rich genes via increased cytoplasmic localization; an effect not observed for GC-rich genes [160] (Fig.…”

Section: Regulation Of Transcription and Splicingmentioning

confidence: 90%

The effects of codon bias and optimality on mRNA and protein regulation

Hia

Takeuchi

2020

Cell. Mol. Life Sci.

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The central dogma of molecular biology entails that genetic information is transferred from nucleic acid to proteins. Notwithstanding retro-transcribing genetic elements, DNA is transcribed to RNA which in turn is translated into proteins. Recent advancements have shown that each stage is regulated to control protein abundances for a variety of essential physiological processes. In this regard, mRNA regulation is essential in fine-tuning or calibrating protein abundances. In this review, we would like to discuss one of several mRNAintrinsic features of mRNA regulation that has been gaining traction of recentcodon bias and optimality. Specifically, we address the effects of codon bias with regard to codon optimality in several biological processes centred on translation, such as mRNA stability and protein folding among others. Finally, we examine how different organisms or cell types, through this system, are able to coordinate physiological pathways to respond to a variety of stress or growth conditions.

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Section: Regulation Of Transcription and Splicingmentioning

confidence: 90%

The effects of codon bias and optimality on mRNA and protein regulation

Hia

Takeuchi

2020

Cell. Mol. Life Sci.

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Sequence determinants and evolution of constitutive and alternative splicing in yeast species

Schirman

Yakhini²,

Dahan

et al. 2020

Preprint

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mRNA splicing is one of the key processes in eukaryotic gene expression. Most Intron-containing genes are constitutively spliced, and hence must undergo splicing in order to produce a functional mature mRNA. Therefore, regulation of splicing efficiency greatly affects broader gene expression regulation. Here we use a large synthetic oligo library of ~25,000 variants to explore how different intronic sequence determinants affect splicing efficiency and mRNA expression levels in yeast. We found that the three splice sites (donor, acceptor, and branching point) differ in how deviations from the consensus sequence affect functionality. We also use intronic sequences from other yeast species with modified splicing machinery to show that intron architecture has co-evolved with the splicing machinery to adapt to the presence or absence of a specific splicing factor. Finally, we show that synthetic sequences containing two introns give rise to diverse RNA isoforms, which enables us to elucidate intronic features that control and enable alternative splicing. Our study reveals novel mechanisms by which introns are shaped in evolution to allow cells to regulate their transcriptome.

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Evidence for strong mutation bias towards, and selection against, T/U content in SARS-CoV2: implications for attenuated vaccine design

Rice

Castillo-Morales

et al. 2020

Preprint

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Large-scale re-engineering of synonymous sites is a promising strategy to generate attenuated viruses for vaccines. Attenuation typically relies on de-optimisation of codon pairs and maximization of CpG dinculeotide frequencies. So as to formulate evolutionarily-informed attenuation strategies, that aim to force nucleotide usage against the estimated direction favoured by selection, here we examine available whole-genome sequences of SARS-CoV2 to infer patterns of mutation and selection on synonymous sites. Analysis of mutational profiles indicates a strong mutation bias towards T withconcomitant selection against T. Accounting for dinucleotide effects reinforces this conclusion, observed TT content being a quarter of that expected under neutrality. A significantly different mutational profile at CDS sites that are not 4-fold degenerate is consistent with contemporaneous selection against T mutations more widely. Although selection against CpG dinucleotides is expected to drive synonymous site G+C content below mutational equilibrium, observed G+C content is slightly above equilibrium, possibly because of selection for higher expression. Consistent with gene-specific selection against CpG dinucleotides, we observe systematic differences of CpG content between SARS-CoV2 genes. We propose an evolutionarily informed gene-bespoke approach to attenuation that, unusually, seeks to increase usage of the already most common synonymous codons. Comparable analysis of H1N1 and Ebola finds that GC3 deviated from neutral equilibrium is not a universal feature, cautioning against

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Codon usage and splicing jointly influence mRNA localization

Cited by 3 publications

References 57 publications

The effects of codon bias and optimality on mRNA and protein regulation

The effects of codon bias and optimality on mRNA and protein regulation

Sequence determinants and evolution of constitutive and alternative splicing in yeast species

Evidence for strong mutation bias towards, and selection against, T/U content in SARS-CoV2: implications for attenuated vaccine design

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