Dataset Information

ITARGEX analysis of yeast deletome reveals novel regulators of transcriptional buffering in S phase and protein turnover

ABSTRACT: Integrating omics data with quantification of biological traits provides unparalleled opportunities for discovery of genetic regulators by in silico inference. However, current approaches to analyze genetic-perturbation screens are limited by their reliance on annotation libraries for prioritization of hits and subsequent targeted experimentation. Here, we present iTARGEX (identification of Trait-Associated Regulatory Genes via mixture regression using EXpectation maximization), an association framework with no requirement of a priori knowledge of gene function. After creating this tool, we used it to test associations between gene expression profiles and two biological traits in single-gene-deleted budding yeast mutants, including transcription homeostasis during S phase and global protein turnover. For each trait, we discovered novel regulators without prior functional annotations. The functional effects of the novel candidates were then validated experimentally, providing solid evidence for their roles in the respective traits. Hence, we conclude that iTARGEX can reliably identify novel factors involved in given biological traits. As such, it is capable of converting genome-wide observations into causal gene function predictions. Further application of iTARGEX in other contexts is expected to facilitate the discovery of new regulators and provide observations for novel mechanistic hypotheses regarding different biological traits and phenotypes.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Cheng-Fu Kao

LAB HEAD: Cheng-Fu Kao

PROVIDER: PXD024258 | Pride | 2021-09-10

REPOSITORIES: Pride

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Publications

iTARGEX analysis of yeast deletome reveals novel regulators of transcriptional buffering in S phase and protein turnover.

Huang Jia-Hsin JH Liao You-Rou YR Lin Tzu-Chieh TC Tsai Cheng-Hung CH Lai Wei-Yun WY Chou Yang-Kai YK Leu Jun-Yi JY Tsai Huai-Kuang HK Kao Cheng-Fu CF

Nucleic acids research 20210701 13

Integrating omics data with quantification of biological traits provides unparalleled opportunities for discovery of genetic regulators by in silico inference. However, current approaches to analyze genetic-perturbation screens are limited by their reliance on annotation libraries for prioritization of hits and subsequent targeted experimentation. Here, we present iTARGEX (identification of Trait-Associated Regulatory Genes via mixture regression using EXpectation maximization), an association f ...[more]

PMID: 34197604

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Project description:Bacterial adaptation involves extensive cellular reorganization. In particular, growth rate adjustments are associated with substantial modifications of gene expression and mRNA abundance. In this work we aimed to assess the role of mRNA degradation during such variations. A genome-wide transcriptomic-based method was used to determine mRNA half-lives. The model bacterium Lactococcus lactis was used and five growth rates were studied in continuous cultures under isoleucine-limitation and in batch cultures during the adaptation to the isoleucine starvation. During continuous isoleucine-limited growth, the mRNAs of different genes had different half-lives. The stability of most of the transcripts was not constant, and increased as the growth rate decreased. This half-life diversity was analyzed to investigate determinants of mRNA stability. The concentration, length, codon adaptation index and secondary structures of mRNAs were found to contribute to the regulation of mRNA stability in these conditions. However, the growth rate was, by far, the most influential determinant. The respective influences of mRNA degradation and transcription on the regulation of intra-cellular transcript concentration were estimated. The role of degradation on mRNA homeostasis was clearly evidenced: for more than 90 % of the mRNAs studied during continuous isoleucine-limited growth of L. lactis, degradation was antagonistic to transcription. Although both transcription and degradation had, opposite effects,, the mRNA changes in response to growth rate were driven by transcription. Interestingly, degradation control increased during the dynamic adaptation of bacteria as the growth rate reduced due to progressive isoleucine starvation in batch cultures. This work shows that mRNA decay differs between gene transcripts and according to the growth rate. It demonstrates that mRNA degradation is an important regulatory process involved in bacterial adaptation. However, its impact on the regulation of mRNA levels is smaller than that of transcription in the conditions studied. In the study presented here mRNA stabilities were analyzed at 5 growth rates. For each growth rate mRNA levels were measured in a time course experiment following rifampicin addition. At least 12 time points per growth rate are available, including 3 replicates of the zero.

Dataset Information

ITARGEX analysis of yeast deletome reveals novel regulators of transcriptional buffering in S phase and protein turnover

Publications

iTARGEX analysis of yeast deletome reveals novel regulators of transcriptional buffering in S phase and protein turnover.

Similar Datasets

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