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  1. Article ; Online: Modulation of Gene Expression in the Eye with Antisense Oligonucleotides.

    Hu, Jiaxin / Gong, Xin / Fan, Yan / Aguilar, Selina / Rigo, Frank / Prakash, Thahza P / Corey, David R / Mootha, V Vinod

    Nucleic acid therapeutics

    2023  Volume 33, Issue 6, Page(s) 339–347

    Abstract: One advantage of antisense oligonucleotides (ASOs) for drug development is their long-lasting gene knockdown after ... ...

    Abstract One advantage of antisense oligonucleotides (ASOs) for drug development is their long-lasting gene knockdown after administration
    MeSH term(s) Mice ; Animals ; Oligonucleotides, Antisense/genetics ; Oligonucleotides, Antisense/pharmacology ; Retina ; Endothelium, Corneal ; Gene Expression
    Chemical Substances Oligonucleotides, Antisense
    Language English
    Publishing date 2023-11-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2639888-6
    ISSN 2159-3345 ; 2159-3337
    ISSN (online) 2159-3345
    ISSN 2159-3337
    DOI 10.1089/nat.2023.0044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Nuclear Localization of Argonaute is affected by Cell Density and May Relieve Repression by microRNAs.

    Johnson, Krystal C / Kilikevicius, Audrius / Hofman, Cristina / Hu, Jiaxin / Liu, Yang / Aguilar, Selina / Graswich, Jon / Han, Yi / Wang, Tao / Westcott, Jill M / Brekken, Rolf A / Peng, Lan / Karagkounis, Georgios / Corey, David R

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Argonaute protein is associated with post-transcriptional control of cytoplasmic gene expression through miRNA-induced silencing complexes (miRISC). Specific cellular and environmental conditions can trigger AGO protein to accumulate in the nucleus. ... ...

    Abstract Argonaute protein is associated with post-transcriptional control of cytoplasmic gene expression through miRNA-induced silencing complexes (miRISC). Specific cellular and environmental conditions can trigger AGO protein to accumulate in the nucleus. Localization of AGO is central to understanding miRNA action, yet the consequences of AGO being in the nucleus are undefined. We show nuclear enrichment of AGO2 in HCT116 cells grown in two-dimensional culture to high density, HCT116 cells grown in three-dimensional tumor spheroid culture, and human colon tumors. The shift in localization of AGO2 from cytoplasm to nucleus de-represses cytoplasmic AGO2-eCLIP targets that were candidates for canonical regulation by miRISC. Constitutive nuclear localization of AGO2 using an engineered nuclear localization signal increases cell migration. Critical RNAi factors also affect the localization of AGO2. Knocking out an enzyme essential for miRNA biogenesis, DROSHA, depletes mature miRNAs and restricts AGO2 localization to the cytoplasm, while knocking out the miRISC scaffolding protein, TNRC6, results in nuclear localization of AGO2. These data suggest that AGO2 localization and miRNA activity can be regulated depending on environmental conditions, expression of mature miRNAs, and expression of miRISC cofactors. Localization and expression of core miRISC protein machinery should be considered when investigating the roles of miRNAs.
    Language English
    Publishing date 2023-07-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.07.548119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Nuclear localization of Argonaute 2 is affected by cell density and may relieve repression by microRNAs.

    Johnson, Krystal C / Kilikevicius, Audrius / Hofman, Cristina / Hu, Jiaxin / Liu, Yang / Aguilar, Selina / Graswich, Jon / Han, Yi / Wang, Tao / Westcott, Jill M / Brekken, Rolf A / Peng, Lan / Karagkounis, Georgios / Corey, David R

    Nucleic acids research

    2023  Volume 52, Issue 4, Page(s) 1930–1952

    Abstract: Argonaute protein is associated with post-transcriptional control of cytoplasmic gene expression through miRNA-induced silencing complexes (miRISC). Specific cellular and environmental conditions can trigger AGO protein to accumulate in the nucleus. ... ...

    Abstract Argonaute protein is associated with post-transcriptional control of cytoplasmic gene expression through miRNA-induced silencing complexes (miRISC). Specific cellular and environmental conditions can trigger AGO protein to accumulate in the nucleus. Localization of AGO is central to understanding miRNA action, yet the consequences of AGO being in the nucleus are undefined. We show nuclear enrichment of AGO2 in HCT116 cells grown in two-dimensional culture to high density, HCT116 cells grown in three-dimensional tumor spheroid culture, and human colon tumors. The shift in localization of AGO2 from cytoplasm to nucleus de-represses cytoplasmic AGO2-eCLIP targets that were candidates for canonical regulation by miRISC. Constitutive nuclear localization of AGO2 using an engineered nuclear localization signal increases cell migration. Critical RNAi factors also affect the localization of AGO2. Knocking out an enzyme essential for miRNA biogenesis, DROSHA, depletes mature miRNAs and restricts AGO2 localization to the cytoplasm, while knocking out the miRISC scaffolding protein, TNRC6, results in nuclear localization of AGO2. These data suggest that AGO2 localization and miRNA activity can be regulated depending on environmental conditions, expression of mature miRNAs, and expression of miRISC cofactors. Localization and expression of core miRISC protein machinery should be considered when investigating the roles of miRNAs.
    MeSH term(s) Humans ; Argonaute Proteins/metabolism ; Cell Count ; Cytoplasm/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA Interference ; Cell Nucleus/metabolism
    Chemical Substances Argonaute Proteins ; MicroRNAs ; AGO2 protein, human
    Language English
    Publishing date 2023-12-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad1155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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