A novel RNA molecular signature for activation of 2'-5' oligoadenylate synthetase-1
| Autor: | Brenda M. Calderon, Graeme L. Conn, Virginia K. Vachon |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
RNA
Untranslated Biology RNA polymerase III 03 medical and health sciences RNA interference Genetics Consensus sequence 2' 5'-Oligoadenylate Synthetase Humans Nucleotide Motifs 030304 developmental biology RNA Double-Stranded chemistry.chemical_classification 0303 health sciences DNA ligase Innate immune system 2'-5'-Oligoadenylate 030302 biochemistry & molecular biology RNA Molecular biology 3. Good health Cell biology Enzyme Activation RNA silencing Pyrimidines chemistry Mutagenesis RNA Viral |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | Human 2'-5' oligoadenylate synthetase-1 (OAS1) is central in innate immune system detection of cytoplasmic double-stranded RNA (dsRNA) and promotion of host antiviral responses. However, the molecular signatures that promote OAS1 activation are currently poorly defined. We show that the 3'-end polyuridine sequence of viral and cellular RNA polymerase III non-coding transcripts is critical for their optimal activation of OAS1. Potentiation of OAS1 activity was also observed with a model dsRNA duplex containing an OAS1 activation consensus sequence. We determined that the effect is attributable to a single appended 3'-end residue, is dependent upon its single-stranded nature with strong preference for pyrimidine residues and is mediated by a highly conserved OAS1 residue adjacent to the dsRNA binding surface. These findings represent discovery of a novel signature for OAS1 activation, the 3'-single-stranded pyrimidine (3'-ssPy) motif, with potential functional implications for OAS1 activity in its antiviral and other anti-proliferative roles. |
| Databáze: | OpenAIRE |
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