Neurospora crassa
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA290152 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2105980.fastq.gz | Fastqsanger.gz | |||
| SRR2105981.fastq.gz | Fastqsanger.gz | |||
| SRR2105982.fastq.gz | Fastqsanger.gz | |||
| SRR2105983.fastq.gz | Fastqsanger.gz | |||
| SRR2105984.fastq.gz | Fastqsanger.gz |
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Project description:Codon usage bias is a universal feature of eukaryotic and prokaryotic genomes and has been proposed to regulate translation efficiency, accuracy and protein folding based on the assumption that codon usage affects translation dynamics. The role of codon usage in regulating translation, however, is not clear and has been challenged by recent ribosome profiling studies. Here we used a Neurospora cell-free translation system to directly monitor the velocity of mRNA translation. We demonstrated that the use of preferred codons enhances the rate of translation elongation, whereas non-optimal codons slow translation. In addition, codon usage regulates ribosome traffic on the mRNA. These conclusions were supported by ribosome profiling results in vitro and in vivo with substrate mRNAs manipulated to increase signal over background noise. We further show that codon usage plays an important role in regulating protein function by affecting co-translational protein folding. Together, these results resolve a long-standing fundamental question and demonstrate the importance of codon usage on protein folding.
2015-07-18 | GSE71032 | GEO
Project description:Ribosome dynamics during mRNA translation elongation regulate mRNA stability. Yet, known regulators of ribosome transit, such as codon usage, cannot fully explain transcriptome-wide decay rates. Here, we demonstrate that nascent polypeptide folding status modulates elongation rates, with Zuotin (Zuo1) serving as an essential mediator, and this also influences mRNA stability. Using reporter constructs encoding co-translationally unstructured proteins and RNA sequencing under proteotoxic stress, we show that Zuo1 is required for the selective destabilization of transcripts whose nascent peptides fail to fold properly. This process is independent of codon optimality but relies on the co-translational mRNA decay factor Not5, which detects slowed ribosomes. 35S labeling indicates that nascent peptide folding defects correlate with reduced elongation rates in a Zuo1-dependent manner, and ribosome profiling reveals that global protein misfolding induces Zuo1-dependent ribosome pausing. These findings position Zuo1 as a key mediator linking nascent peptide folding status to ribosome dynamics and mRNA stability. Furthermore, this work suggests an expanded role for Not5 beyond codon optimality sensing.
2026-07-24 | GSE319659 | GEO
Project description:Ribosome profiling data reports on the distribution of translating ribosomes, at steady-state, with codon-level resolution. We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast. We show that neither elongation rate nor translational efficiency is improved by experimental manipulation of the abundance or body sequence of the rare AGG tRNA. Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate-reducing signals at gene start. This suggests that correlation between codon bias and efficiency arises as selection for codons to utilize translation machinery efficiently in highly translated genes. We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation. We test whether tRNA abundance affects elongation or translation efficiency by changing the tRNA levels through deletion or over expression and measuring the ribosomal dwell time at each codon using a robust statistical method that accounts for flow conservation.
2015-01-05 | E-GEOD-63789 | biostudies-arrayexpress
Project description:Protein folding in vivo is biologically tuned to minimize off-pathway events and optimize native folding outcomes. A key factor in this process is biased synonymous codon usage, in which synonymous codons modulate local translation rate while maintaining the native amino acid sequence. Here, we demonstrate that native codon usage within the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) induces a translational pause during a critical window of synthesis that is important for CFTR folding, processing, and function. Eliminating this pause by substituting synonymous codons increased the aggregation propensity of immature CFTR and induced conformational and functional changes that persisted during CFTR processing and plasma membrane expression. Interestingly, the resulting mature CFTR protein at the plasma membrane exhibited enhanced ATP-dependent chloride channel gating. Thus, during protein synthesis, cotranslational events dictated by codon usage can imprint persistent conformational and functional properties upon CFTR. Our findings suggest that CFTR codon usage has evolved and adapted to balance a compromise between protein aggregation and a modest loss of channel function.
2025-08-29 | GSE305005 | GEO
Project description:Ribosome dynamics during mRNA translation elongation regulate mRNA stability. Yet, known regulators of ribosome transit, such as codon usage, cannot fully explain transcriptome-wide decay rates. Here, we demonstrate that nascent polypeptide folding modulates elongation rates, with Zuotin (Zuo1) serving as an essential mediator. Using reporter constructs encoding co-translationally unstructured proteins and RNA sequencing under proteotoxic stress, we show that Zuo1 is required for selective destabilization of transcripts whose nascent peptides fail to fold properly. This process relies on the co-translational mRNA decay factor Not5, which detects slowed ribosomes. 35S labeling indicates that nascent peptide folding defects correlate with reduced elongation rates in a Zuo1-dependent manner, and ribosome profiling reveals that global protein misfolding induces Zuo1-dependent ribosome pausing. These findings position Zuo1 as a key mediator linking nascent peptide folding status to ribosome dynamics and mRNA stability. Furthermore, this work suggests an expanded role for Not5 beyond codon optimality sensing.
2023-06-01 | GSE151370 | GEO
Project description:Ribosome dynamics during mRNA translation elongation regulate mRNA stability. Yet, codon usage, a known regulator of ribosome transit, cannot fully explain transcriptome-wide decay rates. Here, we demonstrate that nascent polypeptide folding modulates elongation rates, with Zuotin (Zuo1) serving as an essential mediator. Using reporter constructs and RNA sequencing, we show that Zuo1 is essential for the selective destabilization of transcripts encoding co-translationally misfolded proteins. This process is independent of codon optimality but relies on co-translational mRNA decay factor Not5, which detects slowed ribosomes. Ribosome profiling reveals that global protein misfolding induces Zuo1-dependent ribosome stalling. 35S labeling confirms that nascent peptide misfolding directly slows elongating ribosomes in a Zuo1-dependent manner. These findings highlight Zuo1 as a pivotal mediator linking nascent peptide folding to ribosome dynamics and thereby mRNA stability, unveiling a novel mechanism of mRNA regulation driven by protein products. Furthermore, this work expands Not5’s role beyond codon optimality sensing.
2026-06-01 | GSE290416 | GEO
Project description:Ribosome profiling data reports on the distribution of translating ribosomes, at steady-state, with codon-level resolution. We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast. We show that neither elongation rate nor translational efficiency is improved by experimental manipulation of the abundance or body sequence of the rare AGG tRNA. Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate-reducing signals at gene start. This suggests that correlation between codon bias and efficiency arises as selection for codons to utilize translation machinery efficiently in highly translated genes. We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation.
2015-01-05 | GSE63789 | GEO
Project description:A major determinant of mRNA half-life is the codon-dependent rate of translational elongation. How the processes of translational elongation and mRNA decay communicate is unclear. In this study we establish that the DEAD-box helicase Dhh1p is the sensor of codon optimality (i.e. translational elongation rate) that targets an mRNA for decay. First, we find that mRNAs whose translation elongation rate is slowed by inclusion of non-optimal codons are specifically degraded in a DHH1-dependent manner. Biochemical experiments show that Dhh1p is preferentially associated with mRNAs with suboptimal codon choice. We find that these effects on mRNA decay are sensitive to the number of slow moving ribosomes on an mRNA. Using a tethering system, we establish that non-optimal mRNAs become preferentially saturated with ribosomes when Dhh1p is bound. Moreover, over-expression of Dhh1p leads to the accumulation of ribosomes specifically on mRNAs with low codon optimality in ribosome profiling experiments. Lastly, Dhh1p physically interacts with ribosomes in vivo. Together, these data argue that Dhh1p is a sensor for ribosome speed, targeting an mRNA for repression and subsequent decay.
2016-05-11 | GSE81269 | GEO
Project description:Background Cells regulate protein synthesis in response to fluctuating nutrient availability through mechanisms that affect both translation initiation and elongation. Branched-chain amino acids, leucine, isoleucine, and valine, are essential nutrients. However, how their depletion affects translation remains largely unclear. Here, we investigate the immediate effects of single, double, and triple branched-chain amino acid deprivation on translational dynamics in NIH3T3 cells using RNA-seq and ribosome profiling. Results All starvation conditions increased ribosome dwell times, with pronounced stalling at all valine codons during valine and triple starvation, whereas leucine and isoleucine starvation produced milder, codon-specific effects. Notably, stalling under isoleucine deprivation largely decreased under triple starvation. Positional enrichment of valine codons near the 5′ end and downstream isoleucine codons potentially contributes to these patterns, suggesting a possible elongation bottleneck that influences translational responses under branched-chain amino acid starvation. The presence of multiple valine stalling sites was associated with decreased protein levels. Finally, codon-specific dwell time changes correlated strongly with patterns of tRNA isoacceptor charging. Conclusions Together, these findings suggest that differential ribosome stalling under branched-chain amino acid starvation reflects a balance between amino acid supply, tRNA charging dynamics, codon position, and stress-response signaling.
2025-09-02 | GSE291653 | GEO
Project description:Background: Cells regulate protein synthesis in response to fluctuating nutrient availability through mechanisms that affect both translation initiation and elongation. Branched-chain amino acids, leucine, isoleucine, and valine, are essential nutrients. However, how their depletion affects translation remains largely unclear. Here, we investigate the immediate effects of single, double, and triple branched-chain amino acid deprivation on translational dynamics in NIH3T3 cells using RNA-seq and ribosome profiling. Results: All starvation conditions increased ribosome dwell times, with pronounced stalling at all valine codons during valine and triple starvation, whereas leucine and isoleucine starvation produced milder, codon-specific effects. Notably, stalling under isoleucine deprivation largely decreased under triple starvation. Positional enrichment of valine codons near the 5' end and downstream isoleucine codons potentially contributes to these patterns, suggesting a possible elongation bottleneck that influences translational responses under branched-chain amino acid starvation. The presence of multiple valine stalling sites was associated with decreased protein levels. Finally, codon-specific dwell time changes correlated strongly with patterns of tRNA isoacceptor charging. Conclusions: Together, these findings suggest that differential ribosome stalling under branched-chain amino acid starvation reflects a balance between amino acid supply, tRNA charging dynamics, codon position, and stress-response signaling.
2025-09-02 | GSE291652 | GEO