TENT5 cytoplasmic non-canonical poly(A) polymerases regulate the innate immune response in animals
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PROVIDER: PRJNA686670 | ENA |
REPOSITORIES: ENA
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Project description:Innate immunity, the first line of host defense against pathogens, is tightly regulated both transcriptionally and post-transcriptionally. Through global transcriptome and proteome analyses in Caenorhabditis elegans, we uncover a modulation of the expression of secreted innate immunity effector proteins by TENT5, one of a recently described family of cytoplasmic poly(A) polymerases. Direct RNA sequencing revealed that TENT-5 polyadenylates mRNAs with signal peptide-encoding sequences, that are translated at the endoplasmic reticulum. Loss of tent-5 function makes worms more susceptible to bacterial infection. Importantly, we demonstrate that the function of TENT-5 in innate immunity is evolutionarily conserved, as its orthologs, TENT5A and TENT5C are induced during macrophage activation and polyadenylate mRNAs, some of which are of genes orthologous to C. elegans TENT-5 targets. In summary, our study reveals cytoplasmic polyadenylation to be a previously unknown component of the post-transcriptional regulation of innate immunity in animals.
2022-10-01 | GSE163549 | GEO
Project description:Innate immunity, the first line of host defense against pathogens, is tightly regulated both transcriptionally and post-transcriptionally. Here, through global transcriptome and proteome analyses in Caenorhabditis elegans, we uncover a modulation of the expression of secreted innate immunity effector proteins by TENT5, one of a recently described family of cytoplasmic poly(A) polymerases. Direct RNA sequencing revealed that TENT-5 polyadenylates mRNAs with signal peptide-encoding sequences, that are translated at the endoplasmic reticulum. Loss of tent-5 function makes worms more susceptible to bacterial infection. Importantly, we demonstrate that the function of TENT-5 in innate immunity is evolutionarily conserved, as its orthologs, TENT5A and TENT5C are induced during macrophage activation and polyadenylate mRNAs, some of which are of genes orthologous to C. elegans TENT-5 targets. In summary, our study reveals cytoplasmic polyadenylation to be a previously unknown component of the post-transcriptional regulation of innate immunity in animals.
2022-05-31 | PXD023238 | Pride
Project description:Comparision of mRNA abundance and translation efficiency mediated by cytoplasmic poly(A) polymerases in C. elegans comparision of different adults treated with RNAi
2014-10-02 | E-GEOD-58918 | biostudies-arrayexpress
Project description:Comparision of mRNA abundance and translation efficiency mediated by cytoplasmic poly(A) polymerases in C. elegans
2014-10-02 | GSE58918 | GEO
Project description:FAM46C is one of the most frequently mutated genes in multiple myeloma (MM) and encodes a protein of unknown function. Using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active cytoplasmic non-canonical poly(A) polymerase, which enhances mRNA stability and gene expression. Moreover, we also found that the reintroduction of active FAM46C into MM cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induced cell death. This is, to our knowledge, the first report that directly associates cytoplasmic poly(A) polymerase with carcinogenesis. Furthermore, our data suggest that the human genome encodes at least eleven non-canonical poly(A) polymerases with four FAM46 family members. Since FAM46 proteins are differentially expressed during development, these proteins may positively regulate transcript stability and translational rate in a tissue-specific manner.
2017-06-30 | GSE83772 | GEO
Project description:TENT5 cytoplasmic non-canonical poly(A) polymerases regulate the innate immune response in animals
| PRJEB40892 | ENA
Project description:Polyadenylation of pre-mRNAs is critical for efficient nuclear export, stability and translation of the mature mRNAs, and thus for gene expression. The bulk of pre-mRNAs are processed by canonical nuclear poly(A) polymerase (PAPS). Both vertebrate and higher-plant genomes encode more than one isoform of this enzyme, and these are co-expressed in different tissues. However, in neither case is it known whether the isoforms fulfil different functions or polyadenylate distinct subsets of pre-mRNAs. Here we show that the three canonical nuclear PAPS isoforms in Arabidopsis are functionally specialized due to their evolutionarily divergent C-terminal domains. A strong loss-of-function mutation in PAPS1 causes a male gametophytic defect, while a weak allele leads to reduced leaf growth that results in part from a constitutive pathogen response. By contrast, plants lacking both PAPS2 and PAPS4 function are viable with wild-type leaf growth. Polyadenylation of SMALL AUXIN UP RNA (SAUR) mRNAs depends specifically on PAPS1 function. The resulting reduction in SAUR activity in paps1 mutants contributes to their reduced leaf growth, providing a causal link between polyadenylation of specific pre-mRNAs by a particular PAPS isoform and plant growth. This suggests the existence of an additional layer of regulation in plant and possibly vertebrate gene expression, where the relative activities of canonical nuclear PAPS isoforms control de novo synthesized poly(A)-tail length and hence expression of specific subsets of mRNAs. Comparing inflorescences and seedlings from paps1-1 mutants and WT. 4 biological replicates for each genotype and tissue.
2013-07-29 | E-GEOD-48821 | biostudies-arrayexpress
Project description:Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3’ end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here we show that the nuclear canonical (PAPalpha and PAPgamma) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression. Deficiencies in the PAPs resulted in perturbations of gene expression, with Star-PAP impacting lowly expressed mRNAs and long-noncoding RNAs to the greatest extent. Importantly, different PASs of a gene are distinctly regulated by different PAPs, leading to widespread relative expression changes of APA isoforms. The location and surrounding sequence motifs of a PAS appear to differentiate its regulation by the PAPs. We show Star-PAP-specific PAS usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN, and the long non-coding RNA NEAT1. The Star-PAP-mediated APA of PTEN is essential for DNA damage-induced increase of PTEN protein levels. Together, our results reveal a PAS-guided and PAP-mediated paradigm for gene expression in response to cellular signaling cues.
2017-06-19 | GSE84461 | GEO
Project description:Polyadenylation of pre-mRNAs is critical for efficient nuclear export, stability and translation of the mature mRNAs, and thus for gene expression. The bulk of pre-mRNAs are processed by canonical nuclear poly(A) polymerase (PAPS). Both vertebrate and higher-plant genomes encode more than one isoform of this enzyme, and these are co-expressed in different tissues. However, in neither case is it known whether the isoforms fulfil different functions or polyadenylate distinct subsets of pre-mRNAs. Here we show that the three canonical nuclear PAPS isoforms in Arabidopsis are functionally specialized due to their evolutionarily divergent C-terminal domains. A strong loss-of-function mutation in PAPS1 causes a male gametophytic defect, while a weak allele leads to reduced leaf growth that results in part from a constitutive pathogen response. By contrast, plants lacking both PAPS2 and PAPS4 function are viable with wild-type leaf growth. Polyadenylation of SMALL AUXIN UP RNA (SAUR) mRNAs depends specifically on PAPS1 function. The resulting reduction in SAUR activity in paps1 mutants contributes to their reduced leaf growth, providing a causal link between polyadenylation of specific pre-mRNAs by a particular PAPS isoform and plant growth. This suggests the existence of an additional layer of regulation in plant and possibly vertebrate gene expression, where the relative activities of canonical nuclear PAPS isoforms control de novo synthesized poly(A)-tail length and hence expression of specific subsets of mRNAs.
2013-07-29 | GSE48821 | GEO
Project description:Cytoplasmic polyadenylation is a mechanism to promote mRNA translation in a wide variety of biological contexts. A canonical complex centered around the conserved RNA-binding protein family CPEB has been shown to be responsible for this process. We have previously reported evidence for an alternative non-canonical, CPEB-independent complex in Drosophila, of which the RNA-interference factor Dicer-2 is a component. Here, we investigate Dicer-2 mRNA targets and protein co-factors in cytoplasmic polyadenylation. Using RIP-Seq analysis we identify hundreds of novel Dicer-2 target transcripts, ~50% of which were previously found as targets of the cytoplasmic poly(A) polymerase Wispy, suggesting widespread roles of Dicer-2 in cytoplasmic polyadenylation. Large-scale immunoprecipitation revealed Ataxin-2 and Twenty-four among the high-confidence interactors of Dicer-2. Functional analysis indicate that both factors form an RNA-independent complex with Dicer-2, and are required for cytoplasmic polyadenylation of Dicer-2 targets. Our results reveal the composition of a novel cytoplasmic polyadenylation complex that operates during Drosophila early embryogenesis.
2022-08-29 | GSE189868 | GEO