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TENT-5 C. elegans and TENT5A/C murine BMDM

ABSTRACT: TENT5 cytoplasmic non-canonical poly(A) polymerases regulate the innate immune response in animals

PROVIDER: PRJEB40892 | ENA |

REPOSITORIES: ENA

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TENT5 cytoplasmic non-canonical poly(A) polymerases regulate the innate immune response in animals

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

The FAM46C gene encodes a non-canonical poly(A) polymerase and acts as an onco-suppressor in multiple myeloma

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.

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Caenorhabditis elegans

Project description:The cytoplasmic poly(A) polymerases GLD-2 and GLD-4 promote general gene expression via distinct mechanisms

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TENT5 cytoplasmic non-canonical poly(A) polymerases regulate the innate immune response in animals

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.

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The cytoplasmic poly(A) polymerases GLD-2 and GLD-4 promote general gene expression via distinct mechanisms

Project description:Comparision of mRNA abundance and translation efficiency mediated by cytoplasmic poly(A) polymerases in C. elegans

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The cytoplasmic poly(A) polymerases GLD-2 and GLD-4 promote general gene expression via distinct mechanisms

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Project description:To investigate sRNAs and mRNAs that are targeted by poly(U) polymerases in C. elegans.

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Sequencing experiments on poly(U) polymerase mutants in C. elegans [mrna]

Project description:To investigate sRNAs and mRNAs that are targeted by poly(U) polymerases in C. elegans.

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2022-10-05 | PXD036610 | Pride

Specialized germline P-bodies are required to specify germ cell fate in C. elegans embryos

Project description:In animals with germ plasm, specification of the germline involves “germ granules”, cytoplasmic condensates that enrich maternal transcripts in the germline founder cells. In C. elegans embryos, P granules enrich maternal transcripts, but surprisingly P granules are not essential for germ cell fate specification. Here we describe a second condensate in the C. elegans germ plasm. Like canonical P-bodies found in somatic cells, “germline P-bodies” contain regulators of mRNA decapping and deadenylation and, in addition, the intrinsically-disordered proteins MEG-1 and MEG-2 and the TIS11-family RNA-binding protein POS-1. Embryos lacking meg-1 and meg-2 do not stabilize P-body components, miss-regulate POS-1 targets, miss-specify the germline founder cell, and do not develop a germline. Our findings suggest that specification of the germ line involves at least two distinct condensates that independently enrich and regulate maternal mRNAs in the germline founder cells.

2022-10-04 | GSE211555 | GEO

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