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

• Published in: Science advances Vol. 8; no. 46; p. eadd9468
• Main Authors: Liudkovska, Vladyslava, Krawczyk, Paweł S, Brouze, Aleksandra, Gumińska, Natalia, Wegierski, Tomasz, Cysewski, Dominik, Mackiewicz, Zuzanna, Ewbank, Jonathan J, Drabikowski, Krzysztof, Mroczek, Seweryn, Dziembowski, Andrzej
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science (AAAS) 16-11-2022; American Association for the Advancement of Science
• Subjects: Biomedicine and Life Sciences; Immunology; Life Sciences; Molecular Biology; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.add9468

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 the expression of secreted innate immunity effector proteins in
. Direct RNA sequencing revealed that multiple mRNAs with signal peptide-encoding sequences have shorter poly(A) tails in
-deficient worms. Those mRNAs are translated at the endoplasmic reticulum where a fraction of TENT-5 is present, implying that they represent its direct substrates. Loss of
makes worms more susceptible to bacterial infection. Notably, the role of TENT-5 in innate immunity is evolutionarily conserved. Its orthologs, TENT5A and TENT5C, are expressed in macrophages and induced during their activation. Analysis of macrophages devoid of TENT5A/C revealed their role in the regulation of secreted proteins involved in defense response. In summary, our study reveals cytoplasmic polyadenylation to be a previously unknown component of the posttranscriptional regulation of innate immunity in animals.