Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Caenorhabditis elegans Mus musculus

PROVIDER: GSE163549 | GEO | 2022/10/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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 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 comparision of different adults treated with RNAi

2014-10-02 | E-GEOD-58918 | biostudies-arrayexpress

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

2014-10-02 | GSE58918 | GEO

Target specificity amongst canonical nuclear poly(A) polymerases in plants modulates organ growth and pathogen response

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

Target specificity amongst canonical nuclear poly(A) polymerases in plants modulates organ growth and pathogen response

2013-07-29 | GSE48821 | GEO

Drosophila Trf4-1 involvement in mRNA and primary miRNA transcription

Project description:Drosophila Trf4-1 is a polyadenylation polymerase or terminal nucleotidyl transferase (PAP/TENT) that has been reported to add poly(A) tails to snRNAs in nucleus or mRNAs in cytoplasm. Here, we found that the loss of Trf4-1 resulted in the reduction of mRNAs and primary miRNAs (pri-miRNAs) in both Drosophila S2 cells and adult flies. Interestingly, the role of Trf4-1 in transcription is independent of its PAP/TENT activity. Moreover, using the chromatin immunoprecipitation assay, we uncovered that the loss of Trf4-1 led to abnormal RNA polymerase II accumulation and reduced H3K4me3 binding in promoter regions.

2019-05-01 | GSE127210 | GEO

Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis

Project description:In the Caenorhabditis elegans germline, thousands of mRNAs are concomitantly expressed with antisense 22G-RNAs, which are loaded into the Argonaute CSR-1. Despite their essential functions for animal fertility and embryonic development, how CSR-1 22G-RNAs are produced remains unknown. Here, we show that CSR-1 slicer activity is primarily involved in triggering the synthesis of small RNAs on the coding sequences of germline mRNAs and post-transcriptionally regulates a fraction of targets. CSR-1-cleaved mRNAs prime the RNA-dependent RNA polymerase, EGO-1, to synthesize 22G-RNAs in phase with ribosome translation in the cytoplasm, in contrast to other 22G-RNAs mostly synthesized in germ granules. Moreover, codon optimality and efficient translation antagonize CSR-1 slicing and 22G-RNAs biogenesis. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy in eukaryotes to regulate small RNA biogenesis and Argonaute targeting

2021-04-23 | PXD020293 | Pride

Targeting DHX9 triggers interferon response and replication stress in Small Cell Lung Cancer [RIP-Seq II]

Project description:Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as “viral mimicry”, has emerged as an effective strategy to convert immunologically “cold” tumors into “hot”. Through a curated CRISPR-based screen of RNA Helicases, we identified DExD/H-box helicase 9 (DHX9) as a potent repressor of double-stranded RNA (dsRNA) in small cell lung cancers (SCLCs). Depletion of DHX9 induced accumulation of cytoplasmic dsRNA and triggered tumor-intrinsic innate immunity. Intriguingly, ablating DHX9 also induced aberrant accumulation of R-loops, which resulted in an increase of DNA damage-derived cytoplasmic DNA and replication stress in SCLCs. In vivo, DHX9 deletion promoted decrease in tumor growth while inducing a more immunogenic tumor microenvironment, invigorating responsiveness to immune checkpoint blockade. These findings suggest that DHX9 is a crucial repressor of tumor-intrinsic innate immunity and replication stress, representing a promising target for SCLC and other “cold” tumors where genomic instability contribute to pathology.

2024-02-01 | GSE247217 | GEO

Targeting DHX9 triggers interferon response and replication stress in Small Cell Lung Cancer [RIP-seq I]

2024-02-01 | GSE244104 | GEO

Targeting DHX9 triggers interferon response and replication stress in Small Cell Lung Cancer [RNA-seq]

2024-02-01 | GSE244103 | GEO