論文 - 詳細
| RRC ID | 45980 |
|---|---|
| 著者 | Guo X, Zhang R, Wang J, Ding SW, Lu R. |
| タイトル | Homologous RIG-I-like helicase proteins direct RNAi-mediated antiviral immunity in C. elegans by distinct mechanisms. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
RNAi-mediated antiviral immunity in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), which encodes the helicase and C-terminal domains homologous to the mammalian retinoic acid inducible gene I (RIG-I)-like helicase (RLH) family of cytosolic immune receptors. Here we show that the antiviral function of DRH-1 requires the RIG-I homologous domains as well as its worm-specific N-terminal domain. We also demonstrate that the helicase and C-terminal domains encoded by either worm DRH-2 or human RIG-I can functionally replace the corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans. Notably, substitutions in a three-residue motif of the C-terminal regulatory domain of RIG-I that physically interacts with viral double-stranded RNA abolish the antiviral activity of C-terminal regulatory domains of both RIG-I and DRH-1 in C. elegans. Genetic analysis revealed an essential role for both DRH-1 and DRH-3 in C. elegans antiviral RNAi targeting a natural viral pathogen. However, Northern blot and small RNA deep sequencing analyses indicate that DRH-1 acts to enhance production of viral primary siRNAs, whereas DRH-3 regulates antiviral RNAi by participating in the biogenesis of secondary siRNAs after Dicer-dependent production of primary siRNAs. We propose that DRH-1 facilitates the acquisition of viral double-stranded RNA by the worm dicing complex for the subsequent processing into primary siRNAs. The strong parallel for the antiviral function of RLHs in worms and mammals suggests that detection of viral double-stranded RNA may activate completely unrelated effector mechanisms or, alternatively, that the mammalian RLHs have a conserved activity to stimulate production of viral siRNAs for antiviral immunity by an RNAi effector mechanism. |
| 巻・号 | 110(40) |
| ページ | 16085-90 |
| 公開日 | 2013-10-1 |
| DOI | 10.1073/pnas.1307453110 |
| PII | 1307453110 |
| PMID | 24043766 |
| PMC | PMC3791698 |
| MeSH | Animals Caenorhabditis elegans / immunology* Caenorhabditis elegans / virology* Caenorhabditis elegans Proteins / immunology Caenorhabditis elegans Proteins / metabolism* DEAD-box RNA Helicases / immunology DEAD-box RNA Helicases / metabolism* Electrophoresis, Polyacrylamide Gel Microscopy, Fluorescence Oligonucleotides / genetics RNA Interference / immunology* RNA, Small Interfering / metabolism RNA, Viral / metabolism* Sequence Analysis, RNA |
| IF | 9.412 |
| 引用数 | 34 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | F1000Research |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1329 |