| First Author | Liudkovska V | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 46 | Pages | eadd9468 |
| PubMed ID | 36383655 | Mgi Jnum | J:337629 |
| Mgi Id | MGI:7397740 | Doi | 10.1126/sciadv.add9468 |
| Citation | Liudkovska V, et al. (2022) TENT5 cytoplasmic noncanonical poly(A) polymerases regulate the innate immune response in animals. Sci Adv 8(46):eadd9468 |
| abstractText | 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 Caenorhabditis elegans. Direct RNA sequencing revealed that multiple mRNAs with signal peptide-encoding sequences have shorter poly(A) tails in tent-5-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 tent-5 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. |
