The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy
Argonautes are highly conserved proteins found in almost all eukaryotes and some bacteria and archaea. In humans, there are eight argonaute proteins evenly distributed across two clades, the Ago clade (AGO1-4) and the Piwi clade (PIWIL1-4). The function of Ago proteins is best characterized by their...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253116303407 |
| _version_ | 1818279071271878656 |
|---|---|
| author | Jason P Ross Zena Kassir |
| author_facet | Jason P Ross Zena Kassir |
| author_sort | Jason P Ross |
| collection | DOAJ |
| description | Argonautes are highly conserved proteins found in almost all eukaryotes and some bacteria and archaea. In humans, there are eight argonaute proteins evenly distributed across two clades, the Ago clade (AGO1-4) and the Piwi clade (PIWIL1-4). The function of Ago proteins is best characterized by their role in RNA interference (RNAi) and cytoplasmic post-transcriptional gene silencing (PTGS) – which involves the loading of siRNA or miRNA into argonaute to direct silencing of genes at the posttranscriptional or translational level. However, nuclear-localized, as opposed to cytoplasmic, argonaute-small RNA complexes may also orchestrate the mechanistically very different process of transcriptional gene silencing, which results in prevention of transcription from a gene locus by the formation of silent chromatin domains. More recently, the role of argonaute in other aspects of epigenetic regulation of chromatin, alternative splicing and DNA repair is emerging. This review focuses on the activity of nuclear-localized short RNA-argonaute complexes in a mammalian setting and discusses recent in vivo studies employing nuclear-directed sRNA for therapeutic interventions. These studies heed the potential development of RNA-based drugs which induce epigenetic changes in the cell. |
| first_indexed | 2024-12-12T23:27:30Z |
| format | Article |
| id | doaj.art-ff1c7dc1528343ce9744487a33bdd993 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-12T23:27:30Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-ff1c7dc1528343ce9744487a33bdd9932022-12-22T00:07:59ZengElsevierMolecular Therapy: Nucleic Acids2162-25312014-01-013C10.1038/mtna.2014.54The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for TherapyJason P Ross0Zena Kassir1CSIRO Food and Nutrition Flagship, Sydney, New South Wales, AustraliaCSIRO Food and Nutrition Flagship, Sydney, New South Wales, AustraliaArgonautes are highly conserved proteins found in almost all eukaryotes and some bacteria and archaea. In humans, there are eight argonaute proteins evenly distributed across two clades, the Ago clade (AGO1-4) and the Piwi clade (PIWIL1-4). The function of Ago proteins is best characterized by their role in RNA interference (RNAi) and cytoplasmic post-transcriptional gene silencing (PTGS) – which involves the loading of siRNA or miRNA into argonaute to direct silencing of genes at the posttranscriptional or translational level. However, nuclear-localized, as opposed to cytoplasmic, argonaute-small RNA complexes may also orchestrate the mechanistically very different process of transcriptional gene silencing, which results in prevention of transcription from a gene locus by the formation of silent chromatin domains. More recently, the role of argonaute in other aspects of epigenetic regulation of chromatin, alternative splicing and DNA repair is emerging. This review focuses on the activity of nuclear-localized short RNA-argonaute complexes in a mammalian setting and discusses recent in vivo studies employing nuclear-directed sRNA for therapeutic interventions. These studies heed the potential development of RNA-based drugs which induce epigenetic changes in the cell.http://www.sciencedirect.com/science/article/pii/S2162253116303407AgoargonautemicroRNAmiRNAnuclearRNAasiRNATGStherapy |
| spellingShingle | Jason P Ross Zena Kassir The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy Molecular Therapy: Nucleic Acids Ago argonaute microRNA miRNA nuclear RNAa siRNA TGS therapy |
| title | The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy |
| title_full | The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy |
| title_fullStr | The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy |
| title_full_unstemmed | The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy |
| title_short | The Varied Roles of Nuclear Argonaute-Small RNA Complexes and Avenues for Therapy |
| title_sort | varied roles of nuclear argonaute small rna complexes and avenues for therapy |
| topic | Ago argonaute microRNA miRNA nuclear RNAa siRNA TGS therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2162253116303407 |
| work_keys_str_mv | AT jasonpross thevariedrolesofnuclearargonautesmallrnacomplexesandavenuesfortherapy AT zenakassir thevariedrolesofnuclearargonautesmallrnacomplexesandavenuesfortherapy AT jasonpross variedrolesofnuclearargonautesmallrnacomplexesandavenuesfortherapy AT zenakassir variedrolesofnuclearargonautesmallrnacomplexesandavenuesfortherapy |