Genome-wide role of codon usage on transcription and identification of potential regulators

Zhao, Fangzhou; Zhou, Zhipeng; Dang, Yunkun; Na, Hyunsoo; Adam, Catherine; Lipzen, Anna; Ng, Vivian; Grigoriev, Igor V.; Liu, Yi

doi:10.1073/pnas.2022590118

Cited by 38 publications

(32 citation statements)

References 49 publications

(67 reference statements)

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“…Our observed tissue-specific protein expression of rare codon-enriched reporters in the testis and brain could be primarily driven at the protein level, but could also be regulated at the level of mRNA (reviewed in Radhakrishnan & Green, 2016). Rare codons can decrease levels of transcription (Zhao et al, 2021; Z. Zhou et al, 2016) or can negatively impact mRNA stability through a growing number of characterized mechanisms and in numerous model systems (Bazzini et al, 2016; Burow et al, 2018; Buschauer et al, 2020; Presnyak et al, 2015; Radhakrishnan et al, 2016; Wu et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

Distinct responses to rare codons in select Drosophila tissues

Allen

Stewart

Rogers

et al. 2022

Preprint

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Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wide screen in Drosophila melanogaster for distinct tissue responses to codon usage bias. These reporters reveal a cliff-like decline of protein expression near the limit of rare codon usage in endogenously expressed Drosophila genes. Near the edge of this limit, however, we find the testis and brain are uniquely capable of expressing rare codon-enriched reporters. We define a new metric of tissue-specific codon usage, the tissue-apparent Codon Adaptation Index, to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis. We further demonstrate a role for rare codons in restricting protein expression of an evolutionarily young gene, RpL10Aa, to the Drosophila testis. Rare codon-mediated restriction of this testis-specific protein is critical for female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.

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Section: Resultsmentioning

confidence: 99%

Distinct responses to rare codons in select Drosophila tissues

Allen

Stewart

Rogers

et al. 2022

Preprint

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“…Use of preferred codons speeds up the local rate of translation elongation while rare codons slow down translation elongation and potentially result in ribosome pausing and premature termination, a mechanism that can affect translation efficiency ( 21 , 23 ). We also showed that codon usage could influence gene expression levels by affecting transcription efficiency ( 13 , 33 , 64 ). These results led us to propose that codon usage represents a code within the genetic codons that regulates both gene expression level and protein structure.…”

Section: Introductionmentioning

confidence: 87%

Codon usage and protein length-dependent feedback from translation elongation regulates translation initiation and elongation speed

Lyu

Yang

Zhao

et al. 2021

Nucleic Acids Research

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Essential cellular functions require efficient production of many large proteins but synthesis of large proteins encounters many obstacles in cells. Translational control is mostly known to be regulated at the initiation step. Whether translation elongation process can feedback to regulate initiation efficiency is unclear. Codon usage bias, a universal feature of all genomes, plays an important role in determining gene expression levels. Here, we discovered that there is a conserved but codon usage-dependent genome-wide negative correlation between protein abundance and CDS length. The codon usage effects on protein expression and ribosome flux on mRNAs are influenced by CDS length; optimal codon usage preferentially promotes production of large proteins. Translation of mRNAs with long CDS and non-optimal codon usage preferentially induces phosphorylation of initiation factor eIF2α, which inhibits translation initiation efficiency. Deletion of the eIF2α kinase CPC-3 (GCN2 homolog) in Neurospora preferentially up-regulates large proteins encoded by non-optimal codons. Surprisingly, CPC-3 also inhibits translation elongation rate in a codon usage and CDS length-dependent manner, resulting in slow elongation rates for long CDS mRNAs. Together, these results revealed a codon usage and CDS length-dependent feedback mechanism from translation elongation to regulate both translation initiation and elongation kinetics.

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“…Actually, the advantage of transcriptional related genes and the actual abundance of nosZ transcript also provide the evidences for supporting the above speculation. Additionally, the prediction of nos genes expression by CAI values [47] further indicated that DM15 possessed the stronger expressed potential than DM22. Thus, the existence of dnr gene in the nos cluster of DM15 would be strongly linked to the stronger N2O reducing abilities in comparison with DM22.…”

Section: Discussionmentioning

confidence: 97%

Insights into the mechnisms of the differential abilities of two N2O reducers, Pseudomonas sp., isolated from paddy soil

Liu

Sheng

Chen

et al. 2021

Preprint

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Microbial reduction of nitrous oxide (N 2 O) in soil plays an important role in mitigating N 2 O emission, and it is the only known biological process for N 2 O sink. However, it is not clear about the mechnisms of differential N 2 O reducing function of N 2 O reducers. In this study, the N 2 O reducing activities and nosZ gene transcript abundance of two N 2 O reducers named P. veronii DM15 (DM15) and P. frederiksbergensis DM22 (DM22) were determined under varied temperature and oxygen concentration conditions, as well as the whole genomes were sequenced by Illumina sequencing. The results showed that DM15 generally exhibited significantly higher abilities in N 2 O reduction than DM22 in regardless of low or high temperature and aerobic or anaerobic conditions. Coincidently, DM15 expressed significantly more nosZ gene transcripts under above environments. Genomic analysis further revealed that DM15 possessed about 30% more transcription related genes than DM22 and the nos cluster of the former contained a transcriptional regulator gene of dnr which not found in that of the later. Additionally, the nos genes of DM15 possessed obviously higher expression potentials (CAI value). In conclusion, the transcriptional regulation of nos gene region would be a crucial factor in determining the differences of N 2 O reducing abilities of the two N 2 O reducing isolates.

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Genome-wide role of codon usage on transcription and identification of potential regulators

Cited by 38 publications

References 49 publications

Distinct responses to rare codons in select Drosophila tissues

Distinct responses to rare codons in select Drosophila tissues

Codon usage and protein length-dependent feedback from translation elongation regulates translation initiation and elongation speed

Insights into the mechnisms of the differential abilities of two N2O reducers, Pseudomonas sp., isolated from paddy soil

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