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MRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability

ABSTRACT: mRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability

PROVIDER: PRJNA932446 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23363954_1.fastq.gz	Fastqsanger.gz
	SRR23363954_2.fastq.gz	Fastqsanger.gz
	SRR23363955_1.fastq.gz	Fastqsanger.gz
	SRR23363955_2.fastq.gz	Fastqsanger.gz
	SRR23363956_1.fastq.gz	Fastqsanger.gz

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mRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability

Project description:Yeast mRNA decapping-activators Pat1 and Dhh1 have been implicated in repressing translation and mRNA degardation in glucose-deprived cells, but the specific mRNAs targeted by each factor and their functions in nutrient replete cells are poorly understood. To test this, we performed ribosome profiling and RNA-Seq in WT, pat1D and pat1Ddhh1D. Further, CAGE-Seq and Rpb1-ChIP Seq were employed to determine their role in decapping mediated degradation of mRNAs

2023-09-27 | GSE224774 | GEO

mRNA decapping activators Pat1 and Dhh1 regulate transcript abundance and translation to tune cellular responses to nutrient availability

2023-10-24 | PXD042828 | Pride

Regulation of transcript abundance and translationny decapping activators Pat1 and Dhh1

Project description:We have examined the roles of yeast mRNA decapping-activators Pat1 and Dhh1 in repressing the translation and abundance of specific mRNAs in nutrient-replete cells using ribosome profiling, RNA-Seq, CAGE analysis of capped mRNAs, RNA Polymerase II ChIP-Seq, and TMT-mass spectrometry of mutants lacking one or both factors. Although the Environmental Stress Response (ESR) is activated in dhh1 and pat1 mutants, hundreds of non-ESR transcripts are elevated in a manner indicating cumulative repression by Pat1 and Dhh1 in WT. These mRNAs show reduced decapping and diminished transcription in the mutants, indicating that impaired mRNA turnover drives transcript derepression in cells lacking Dhh1 or Pat1. mRNA degradation stimulated by Dhh1/Pat1 is not dictated by poor translation nor enrichment for suboptimal codons. Pat1 and Dhh1 also collaborate to reduce translation and protein production from many mRNAs. Transcripts showing concerted translational repression by Pat1/Dhh1 include mRNAs involved in cell adhesion or utilization of the poor nitrogen source allantoin. Pat1/Dhh1 also repress numerous transcripts involved in respiration, catabolism of non-preferred carbon or nitrogen sources, or autophagy; and we obtained evidence for elevated respiration and autophagy in the mutants. Thus, Pat1 and Dhh1 function as post-transcriptional repressors of multiple pathways normally activated only during nutrient limitation.

2023-10-24 | PXD042990 | Pride

Decapping activators Edc3 and Scd6 act redundantly with Dhh1 in nutrient-replete cells to post-transcriptionally repress starvation-induced pathways [ChIP-seq]

Project description:Degradation of many yeast mRNAs involves decapping by Dcp1:Dcp2. Previous studies on decapping activators Edc3 and Scd6 suggested limited roles in promoting mRNA decay in yeast cells. RNA-seq analysis of mutants lacking one or both proteins reveals that Scd6 and Edc3 have largely redundant activities in targeting numerous mRNAs for degradation, which are masked in the single mutants. These transcripts are frequently targeted by decapping activators Dhh1 and Pat1 and the evidence suggests that Scd6/Edc3 act interchangeably to recruit Dhh1 to Dcp2 independently of Pat1. Ribosome profiling shows that redundancy between Scd6 and Edc3 and their functional interactions with Dhh1 and Pat1 extends to translational repression of particular transcripts, including a cohort of poorly translated mRNAs displaying interdependent regulation by all four factors. Scd6/Edc3 also participate with Dhh1/Pat1 in post-transcriptional repression of proteins required for respiration and catabolism of non-optimal carbon sources, which are normally expressed only in limiting glucose. Simultaneously eliminating Scd6/Edc3 increases mitochondrial membrane potential and elevates metabolites of the tricarboxylic acid and glyoxylate cycles critical for growth at low glucose levels. Thus, Scd6/Edc3 act redundantly, in parallel with Dhh1 and in cooperation with Pat1, to adjust gene expression to nutrient availability by controlling mRNA decapping and decay.

2024-10-08 | GSE270789 | GEO

Decapping activators Edc3 and Scd6 act redundantly with Dhh1 in nutrient-replete cells to post-transcriptionally repress starvation-induced pathways [Ribo and RNA-seq]

2024-10-08 | GSE270790 | GEO

RNAi knock down of mRNA decapping co-activators in Drosophila S2 cells

Project description:We analyzed mRNA expression profiles in Drosophila melanogaster S2 cells that had been depleted of proteins known as mRNA decapping co-activators. mRNA decapping is catalyzed by DCP2, and DCP2 activity is stimulated by decapping co-activators. This group of proteins includes DCP1, Hedls (also known as Ge-1), LSm16 (also known as EDC3), rck/p54 (also known as DHH1 or Me31B), Pat1, and the heptameric LSm1-7 complex. We used the RNA interference technology to deplete cultured S2 cells of DCP1 (CG11183), Ge-1 (CG6181), Pat1 (CG5208), LSm16 (CG6311), and LSm1 (CG4279). We used Affymetrix oligonucleotide microarrays to analyze two independent samples for each depletion. We included the following controls: mock RNAi treatment and GFP dsRNA treatment (two profiles each). We also profiled AGO1 (CG6671) depleted cells (3 independent samples). AGO1 is a key protein required for miRNA-mediated gene silencing. We had shown previously that silencing by miRNAs involves decapping of target mRNAs.

2007-09-03 | E-MEXP-1012 | biostudies-arrayexpress

Genome-wilde identification of decapping substrates in the yeast Saccharomyces cervisiae

Project description:To assess the roles of the Dcp2 C-terminal domain and the decapping activators Pat1, Lsm1, and Dhh1 in mRNA decapping, we used RNA-Seq to analyze the expression profiles of yeast cells harboring a truncation of the Dcp2 C-terminal domain, mutations that render Dcp2 catalytically inactive, or deletions of the PAT1, LSM1, and DHH1 genes. Consistent with our recent model for decapping regulation, we found that: i) the Dcp2 C-terminal domain is an effector of both negative and positive regulation and that loss of these control functions causes significant deregulation of mRNA decapping; ii) rather than being global activators of decapping, Pat1, Lsm1, and Dhh1 directly target specific subsets of yeast mRNAs and loss of the functions of each of these factors has substantial indirect consequences for genome-wide mRNA expression; and iii) transcripts targeted by Pat1, Lsm1, and Dhh1 exhibit only partial overlap and, as expected, are targeted to decapping-dependent decay.

2017-12-09 | GSE107841 | GEO

Genome-wilde expression profiling analysis of yeast cells lacking the decapping activator Scd6

Project description:To assess the role of the decapping activator Scd6 in mRNA decay, we used RNA-Seq to analyze the expression profile of yeast cells harboring a deletion of the SCD6 gene. Consistent with our recent model for decapping regulation, we found that Scd6 targets a small number of specific mRNAs in yeast cells. Interestingly, degradation of Scd6-targeted transcripts also requires the functions of the decapping activators Pat1, Lsm1, and Dhh1, suggesting that Scd6 functions together with Pat1, Lsm1, and Dhh1 in promoting mRNA decapping.

2018-05-15 | GSE114428 | GEO

Molecular connection between the TUTase URT1 and decapping activators

Project description:Uridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators including DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6. A conserved Helical Leucine-rich Motif (HLM) within an intrinsically disordered region of URT1 binds to the LSm domain of DCP5. This interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. The combination of in planta and in vitro analyses supports a model that explains how URT1 reduces the accumulation of oligo(A)-tailed mRNAs: first, by connecting decapping factors and second, because 3’ terminal uridines can intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs in Arabidopsis avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb plant growth and development.

2020-05-29 | PXD018672 | Pride

Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability

Project description:Degradation of most yeast mRNAs involves decapping by Dcp1/Dcp2. DEAD-box protein Dhh1 has been implicated as an activator of decapping, and as a translational repressor, but their functions in cells are incompletely understood. We have analyzed these questions by a combination of ribosome profiling, RNA-Seq, CAGE analysis of capped mRNAs.

2023-02-07 | GSE216831 | GEO

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