Argonaute proteins: structures and their endonuclease activity
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Keywords:
Argonaute
RasiRNA
Piwi-interacting RNA
RNA-induced silencing complex
Trans-acting siRNA
RNA Silencing
Metazoans guard their germlines against transposons and other foreign transcripts with PIWI-interacting RNAs (piRNAs). Due to the robust heritability of the silencing initiated by piRNAs in Caenorhabditis elegans (C. elegans), previous screens using C. elegans were strongly biased to uncover members of this pathway in the maintenance process but not in the initiation process. To identify novel piRNA pathway members, we have utilized a sensitized reporter strain which detects defects in initiation, amplification, or regulation of piRNA silencing. Using our reporter, we have identified Integrator complex subunits, nuclear pore components, protein import components, and pre-mRNA splicing factors as essential for piRNA-mediated gene silencing. We found the small nuclear processing cellular machine termed the Integrator complex is required for both type I and type II piRNA production. Notably, we identified a role for nuclear pore and nucleolar components NPP-1/Nup54, NPP-6/Nup160, NPP-7/Nup153, and FIB-1 in promoting the perinuclear localization of anti-silencing CSR-1 Argonaute, as well as a role for Importin factor IMA-3 in nuclear localization of silencing Argonaute HRDE-1. Together, we have shown that piRNA silencing in C. elegans is dependent on evolutionarily ancient RNA processing machinery that has been co-opted to function in the piRNA-mediated genome surveillance pathway.
Piwi-interacting RNA
Argonaute
RNA Silencing
RNA-induced silencing complex
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Argonaute
Trans-acting siRNA
RNA-induced silencing complex
RNA Silencing
Dicer
RNA-induced transcriptional silencing
Piwi-interacting RNA
RasiRNA
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Small regulatory RNAs, including siRNA (short interfering RNA), miRNA (microRNA), piRNA (piwi interacting RNA), and hsRNA (heterochromatin associated small RNA), have been the hot frontier of life sciences in the past few years, and it is becoming more and more apparent that these small molecules have key regulatory functions. Small RNAs trigger various forms of sequence specific gene silencing, commonly referred to as RNA silencing, such as RNA interference (RNAi), translational repression, and heterochromatin formation in all higher eukaryotes and play important roles in cellular processes as diverse as development, stress response, or transposon silencing. Soon after the discovery of small regulatory RNAs, members of the RNase III family and Argonaute protein family, some RNA binding proteins, and etc., were identified as their major cellular protein interactors and involved in the biogenesis and various cellular functions of small RNAs. This review summaries the understanding of the structures and functions of the important components in small RNA-induced gene-silencing pathways.
Argonaute
RasiRNA
RNA-induced silencing complex
Trans-acting siRNA
Piwi-interacting RNA
RNA-induced transcriptional silencing
RNA Silencing
Small nucleolar RNA
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Metazoans guard their germlines against transposons and other foreign transcripts with PIWI-interacting RNAs (piRNAs). Due to the robust heritability of the silencing initiated by piRNAs in C.elegans , previous screens using Caenorhabditis elegans were strongly biased to uncover members of this pathway in the maintenance process but not in the initiation process. To identify novel piRNA pathway members, we have utilized a sensitized reporter strain which detects defects in initiation, amplification, or regulation of piRNA silencing. Using our reporter, we have identified Integrator complex subunits, nuclear pore components, protein import components, and pre-mRNA splicing factors as essential for piRNA-mediated gene silencing. We found the snRNA processing cellular machine termed the Integrator complex is required for both type I and type II piRNA production. Notably, we identified a role for nuclear pore and nucleolar components in promoting the perinuclear localization of anti-silencing CSR-1 Argonaute, as well as a role for Importin factor IMA-3 in nuclear localization of silencing Argonaute HRDE-1. Together, we have shown that piRNA silencing is dependent on evolutionarily ancient RNA processing machinery that has been co-opted to function in the piRNA mediated genome surveillance pathway.
Piwi-interacting RNA
RNA Silencing
Argonaute
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SUMMARY P granules are perinuclear condensates in C. elegans germ cells proposed to serve as hubs for self/non-self RNA discrimination by Argonautes. We report that a mutant ( meg-3 meg-4 ) that does not assemble P granules in primordial germ cells loses competence for RNA-interference over several generations and accumulates silencing small RNAs against hundreds of endogenous genes, including the RNA-interference genes rde-11 and sid-1. In wild-type, rde-11 and sid-1 transcripts are heavily targeted by piRNAs, accumulate in P granules, but maintain expression. In the primordial germ cells of meg-3 meg-4 mutants, rde-11 and sid-1 transcripts disperse in the cytoplasm with the small RNA biogenesis machinery, become hyper-targeted by secondary sRNAs, and are eventually silenced. Silencing requires the PIWI-class Argonaute PRG-1 and the nuclear Argonaute HRDE-1 that maintains trans-generational silencing of piRNA targets. These observations support a “safe harbor” model for P granules in protecting germline transcripts from piRNA-initiated silencing.
Piwi-interacting RNA
Argonaute
RasiRNA
RNA-induced silencing complex
Trans-acting siRNA
RNA Silencing
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RNA interference is a process through which double-stranded RNA(dsRNA) induces the sequence-specific posttranscriptional silencing of gene. Argonaute proteins consists of a highly-conserved family with many members. They are the core component of RNA-induced silencing complex (RISC) essential for RNAi. Argonaute proteins selectively recruit miRNAs and siRNAs and also interact with Dicers. Their PIWI box interacts directly with the RNaseⅢ domain of Dicer. The interaction between PIWI and Dicer may facilitate the release of miRNA/siRNA. Furthermore, argonaute proteins may be the source of endonuclease activity in RNAi.
Argonaute
Dicer
RasiRNA
RNA-induced silencing complex
Piwi-interacting RNA
Trans-acting siRNA
RNA Silencing
RNA-induced transcriptional silencing
Cite
Citations (1)
Piwi-interacting RNA
Argonaute
RasiRNA
RNA-induced silencing complex
Trans-acting siRNA
RNA Silencing
Cite
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Argonaute
Trans-acting siRNA
RasiRNA
RNA-induced silencing complex
Piwi-interacting RNA
Dicer
RNA Silencing
Cite
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Argonaute
RasiRNA
Piwi-interacting RNA
Trans-acting siRNA
RNA-induced silencing complex
RNA Silencing
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Citations (56)
Argonaute
RasiRNA
Trans-acting siRNA
RNA-induced silencing complex
RNA Silencing
Piwi-interacting RNA
RNA-induced transcriptional silencing
Cite
Citations (9)