TENT5 cytoplasmic noncanonical poly(A) polymerases regulate the innate immune response in animals

• DOI: 10.1126/sciadv.add9468
• Publication Date: 2022-11-16T18:58:34Z
• Authors: Vladyslava Liudko...; Paweł S. Krawczyk; Aleksandra Brouze; Natalia Gumińska; Tomasz Wegierski; Dominik Cysewski; Zuzanna Mackiewicz; Jonathan J. Ewbank; Krzysztof Drabiko...; Seweryn Mroczek; Andrzej Dziembowski
• Keywords: Proteome

Innate immunity is the first line of host defense against pathogens. Here, through global transcriptome and proteome analyses, we uncover that newly described cytoplasmic poly(A) polymerase TENT-5 (terminal nucleotidyltransferase 5) enhances expression secreted innate effector proteins in Caenorhabditis elegans . Direct RNA sequencing revealed multiple mRNAs with signal peptide–encoding sequences have shorter tails tent-5 –deficient worms. Those are translated at endoplasmic reticulum where a fraction present, implying they represent its direct substrates. Loss makes worms more susceptible to bacterial infection. Notably, role evolutionarily conserved. Its orthologs, TENT5A TENT5C, expressed macrophages induced during their activation. Analysis devoid TENT5A/C regulation involved response. In summary, our study reveals polyadenylation be previously unknown component posttranscriptional animals.