Structural recognition of the mRNA 3’ UTR by PUF-8 restricts the lifespan of C. elegans
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PROVIDER: PRJNA693156 | ENA |
REPOSITORIES: ENA
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Project description:The molecular mechanisms of aging are unsolved and fascinating fundamental biological questions. Caenorhabditis elegans is an ideal model organism for investigating aging. PUF-8, a PUF (Pumilio and FBF) protein in C. elegans, is crucial for germline development through binding to the 3’ untranslated regions (3’ UTR) in the mRNA of target genes. Recently, PUF-8 was reported to alter mitochondrial dynamics and mitophagy by regulating MFF, a mitochondrial fission factor, and subsequently regulate longevity. Here, we determined the crystal structure of the PUF domain of PUF-8 with an RNA substrate. Mutagenesis experiments were performed to alter PUF-8 recognition of its target mRNAs. We generate these mutations in C. elegans, those mutations reduced the fertility and extended the lifespan. We deep sequenced total mRNAs from wild-type and puf-8 mutant worms and conducted in vitro RNA pull-down experiments. Six PUF-8 regulated genes were identified, in which their mRNA 3’ UTRs contain at least one PUF-binding element (PBE). One of the six genes, pqm-1, is crucial for lipid storage and aging process. Knockdown of pqm-1 could revert the lifespan extension of puf-8(-) animals. Therefore, PUF-8 may regulate the lifespan of C. elegans via modulating pqm-1-related pathways
2021-05-01 | GSE165061 | GEO
Project description: Not available
| S-EPMC8464079 | biostudies-literature
Project description:Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response
| PRJNA416003 | ENA
Project description:Expanding the binding specificity for RNA recognition by a PUF domain
2021-07-28 | GSE152452 | GEO
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-11-09 | GSE140160 | GEO
Project description:Functional data indicate that specific histone modification enzymes can be key to longevity in Caenorhabditis elegans, but epigenetic mechanisms of lifespan regulation are not well understood. In this study, we profiled the genome-wide pattern of tri-methylation of lysine 36 on histone 3 (H3K36me3) in the somatic cells of young and old C. elegans. We revealed a new role of H3K36me3 in maintaining gene expression stability through aging with important consequence on longevity. We found that genes with dramatic expression change during aging are marked with low or even undetectable levels of H3K36me3 in their gene-bodies, irrespective of their corresponding mRNA abundance. Importantly, inactivation of the methyltransferase met-1 resulted in a decrease in global H3K36me3 marks, an increase in mRNA expression change with age, and a shortened lifespan, suggesting a causative role of the H3K36me3 marking in modulating age-dependent gene expression stability and longevity. We performed genome-wide mapping of histone H3 and H3K36me3 in young (D2A) and old (D12A) C.elegans somatic cells by ChIP-seq in glp-1(e2141). mRNA-seq was performed in young (D2A) and old (D12A) glp-1(e2141) somatic cells to identify mRNA expression change during aging from D2A to D12A.
2015-04-01 | E-GEOD-62720 | biostudies-arrayexpress
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-12-03 | GSE141306 | GEO
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-12-13 | GSE141973 | GEO
Project description:We have performed a comprehensive analysis of the involvement of histone H3 and H4 residues in the regulation of chronological lifespan in yeast. Residues where substitution resulted in the most pronounced lifespan extension are all on the exposed face of the nucleosome, with the exception of H3E50, which is present on the lateral surface, between two DNA gyres. Other residues that had a more modest effect on lifespan extension were concentrated at the extremities of the H3-H4 dimer, suggesting a role in stabilizing the dimer in its nucleosome frame. Residues implicated in a reduced lifespan were buried in the histone handshake motif, suggesting that these mutations destabilize the octamer structure. All residues exposed on the disk and that caused lifespan extension are known to interact with Sir3. We find that substitution of H4K16 and H4H18 cause Sir3 to redistribute from telomeres and silent mating loci to secondary positions, often enriched for Rap1 or Abf1 binding sites, whereas H3E50 does not. The redistributed Sir3 cause transcriptional repression at most of the new loci, including of genes where null mutants were previously shown to extend chronological lifespan. The transcriptomic profiles of H4K16 and H4H18 mutant strains are very similar, and compatible with a DNA replication stress response. This is distinct from the transcriptomic profile of H3E50, which matches strong induction of oxidative phosphorylation. We propose that different clusters of H3 and H4 residues are involved in either binding to non-histone proteins, or in destabilizing the association of the nucleosome DNA, or disrupting binding of a H3-H4 dimer in the nucleosome, or disturbing the structural stability of the octamer, each category impacting on chronological lifespan through a different path.
2019-12-03 | GSE141317 | GEO
Project description:We used an in vitro pool based strategy to probe the sequence and structural requirements for mRNA target recognition by the yeast tRNA pseudouridine synthase Pus1.
2019-08-14 | GSE99487 | GEO