Ghosh, Souvik and Guimaraes, Joao C. and Lanzafame, Manuela and Schmidt, Alexander and Syed, Afzal Pasha and Dimitriades, Beatrice and Boersch, Anastasiya and Ghosh, Shreemoyee and Mittal, Nitish and Montavon, Thomas and Correia, Ana Luisa and Danner, Johannes and Meister, Gunter and Terracciano, Luigi M. and Pfeffer, Sebastien and Piscuoglio, Salvatore and Zavolan, Mihaela (2020) Prevention of dsRNA-induced interferon signaling by AGO1x is linked to breast cancer cell proliferation. EMBO JOURNAL, 39 (18): e103922. ISSN 0261-4189, 1460-2075
Full text not available from this repository. (Request a copy)Abstract
Translational readthrough, i.e., elongation of polypeptide chains beyond the stop codon, was initially reported for viral RNA, but later found also on eukaryotic transcripts, resulting in proteome diversification and protein-level modulation. Here, we report that AGO1x, an evolutionarily conserved translational readthrough isoform of Argonaute 1, is generated in highly proliferative breast cancer cells, where it curbs accumulation of double-stranded RNAs (dsRNAs) and consequent induction of interferon responses and apoptosis. In contrast to other mammalian Argonaute protein family members with primarily cytoplasmic functions, AGO1x exhibits nuclear localization in the vicinity of nucleoli. We identify AGO1x interaction with the polyribonucleotide nucleotidyltransferase 1 (PNPT1) and show that the depletion of this protein further augments dsRNA accumulation. Our study thus uncovers a novel function of an Argonaute protein in buffering the endogenous dsRNA-induced interferon responses, different than the canonical function of AGO proteins in the miRNA effector pathway. As AGO1x expression is tightly linked to breast cancer cell proliferation, our study thus suggests a new direction for limiting tumor growth.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DOUBLE-STRANDED-RNA; PROTEIN-KINASE PKR; WIDE IDENTIFICATION; HOST-RESISTANCE; HUMAN ARGONAUTE; GENE; TARGET; APOPTOSIS; READTHROUGH; TERMINATION; Argonaute 1; breast cancer; endogenous dsRNA; interferon response; translation readthrough |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2021 12:20 |
| Last Modified: | 11 Mar 2021 12:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43793 |
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