Selective gene expression maintains human tRNA anticodon pools during differentiation
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ABSTRACT:
PROVIDER: PRJNA947519 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23939400_1.fastq.gz | Fastqsanger.gz | |||
| SRR23939400_2.fastq.gz | Fastqsanger.gz | |||
| SRR23939401_1.fastq.gz | Fastqsanger.gz | |||
| SRR23939401_2.fastq.gz | Fastqsanger.gz | |||
| SRR23939402_1.fastq.gz | Fastqsanger.gz |
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Project description:Transfer RNAs are required for translating genetic information into protein sequence. The human genome contains hundreds of tRNA genes, many of which in multiple copies. How their expression is regulated to control functional tRNA levels is unknown. Here, we combined quantitative tRNA profiling and ChIP-Seq to measure tRNA expression upon differentiation of human induced pluripotent stem cells (hiPSC) into neuronal and cardiac cells. We find that tRNA transcript pools vary substantially, while the abundance of tRNAs with distinct anticodons, which governs decoding rates, is more stable among cell types. Mechanistically, RNA Polymerase III (Pol III) samples a wide range of tRNA genes in hiPSC and becomes constrained to a housekeeping subset upon differentiation. This is mediated by diminished mTOR signaling, which activates the Pol III repressor MAF1. Our data rationalize how tRNA anticodon pools are buffered in different cellular contexts and reveal that mTOR activity drives selective tRNA expression.
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Project description:Transfer RNAs are essential for translating genetic information into proteins. The human genome contains hundreds of predicted tRNA genes, many in multiple copies. How their expression is regulated to control tRNA repertoires is unknown. Here we combined quantitative tRNA profiling and chromatin immunoprecipitation with sequencing to measure tRNA expression following the differentiation of human induced pluripotent stem cells into neuronal and cardiac cells. We find that tRNA transcript levels vary substantially, whereas tRNA anticodon pools, which govern decoding rates, are more stable among cell types. Mechanistically, RNA polymerase III transcribes a wide range of tRNA genes in human induced pluripotent stem cells but on differentiation becomes constrained to a subset we define as housekeeping tRNAs. This shift is mediated by decreased mTORC1 signalling, which activates the RNA polymerase III repressor MAF1. Our data explain how tRNA anticodon pools are buffered to maintain decoding speed across cell types and reveal that mTORC1 drives selective tRNA expression during differentiation.
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Project description:Transfer RNAs are required for translating genetic information into protein sequence. The human genome contains hundreds of tRNA genes, many of which in multiple copies. How their expression is regulated to control functional tRNA levels is unknown. Here, we combined quantitative tRNA profiling and ChIP-Seq to measure tRNA expression upon differentiation of human induced pluripotent stem cells (hiPSC) into neuronal and cardiac cells. We find that tRNA transcript pools vary substantially, while the abundance of tRNAs with distinct anticodons, which governs decoding rates, is more stable among cell types. Mechanistically, RNA Polymerase III (Pol III) samples a wide range of tRNA genes in hiPSC and becomes constrained to a housekeeping subset upon differentiation. This is mediated by diminished mTOR signaling, which activates the Pol III repressor MAF1. Our data rationalize how tRNA anticodon pools are buffered in different cellular contexts and reveal that mTOR activity drives selective tRNA expression.
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Project description:Transfer RNAs are required for translating genetic information into protein sequence. The human genome contains hundreds of tRNA genes, many of which in multiple copies. How their expression is regulated to control functional tRNA levels is unknown. Here, we combined quantitative tRNA profiling and ChIP-Seq to measure tRNA expression upon differentiation of human induced pluripotent stem cells (hiPSC) into neuronal and cardiac cells. We find that tRNA transcript pools vary substantially, while the abundance of tRNAs with distinct anticodons, which governs decoding rates, is more stable among cell types. Mechanistically, RNA Polymerase III (Pol III) samples a wide range of tRNA genes in hiPSC and becomes constrained to a housekeeping subset upon differentiation. This is mediated by diminished mTOR signaling, which activates the Pol III repressor MAF1. Our data rationalize how tRNA anticodon pools are buffered in different cellular contexts and reveal that mTOR activity drives selective tRNA expression.
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Project description:Transfer RNAs are required for translating genetic information into protein sequence. The human genome contains hundreds of tRNA genes, many of which in multiple copies. How their expression is regulated to control functional tRNA levels is unknown. Here, we combined quantitative tRNA profiling and ChIP-Seq to measure tRNA expression upon differentiation of human induced pluripotent stem cells (hiPSC) into neuronal and cardiac cells. We find that tRNA transcript pools vary substantially, while the abundance of tRNAs with distinct anticodons, which governs decoding rates, is more stable among cell types. Mechanistically, RNA Polymerase III (Pol III) samples a wide range of tRNA genes in hiPSC and becomes constrained to a housekeeping subset upon differentiation. This is mediated by diminished mTOR signaling, which activates the Pol III repressor MAF1. Our data rationalize how tRNA anticodon pools are buffered in different cellular contexts and reveal that mTOR activity drives selective tRNA expression.
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Proteins begin to fold as they emerge from translating ribosomes. The kinetics of ribosome transit along a given mRNA can influence nascent chain folding, but the extent to which individual codon translation rates impact proteome integrity remains unknown. Here, we show that slower decoding of discrete codons elicits widespread protein aggregation in vivo. Using ribosome profiling, we find that loss of anticodon wobble uridine (U34) modifications in a subset of tRNAs leads to ribosome pausing at their cognate codons in S. cerevisiae and C. elegans. Yeast cells lacking U34 modifications exhibit gene expression hallmarks of proteotoxic stress and accumulate aggregates of endogenous proteins with key cellular functions. Moreover, these cells are severely compromised in clearing stress-induced protein aggregates. Overexpression of hypomodified tRNAs alleviates ribosome pausing, concomitantly restoring protein homeostasis. Our findings demonstrate that modified U34 is an evolutionarily conserved accelerator of decoding and reveal an unanticipated role for tRNA anticodon modifications in maintaining proteome integrity. Ribosome profiling of wild-type and tRNA modification-deficient yeast and nematodes. Yeast samples were generated in various growth conditions (rich medium versus stress induced by treatment with diamide or rapamycin) and paired mRNA-Seq was performed on a subset of samples. Dataset contains three biological replicates for yeast samples and two biological replicates for nematode samples.
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