Hsc70/Hsp90 Chaperone Machinery Mediates ATP-Dependent RISC Loading of Small RNA Duplexes
Small silencing RNAs—small interfering RNAs (siRNAs) or microRNAs (miRNAs)—direct posttranscriptional gene silencing of their mRNA targets as guides for the RNA-induced silencing complex (RISC). Both siRNAs and miRNAs are born double stranded. Surprisingly, loading these small RNA duplexes into Argo...
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Published in | Molecular cell Vol. 39; no. 2; pp. 292 - 299 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
30.07.2010
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Subjects | |
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Abstract | Small silencing RNAs—small interfering RNAs (siRNAs) or microRNAs (miRNAs)—direct posttranscriptional gene silencing of their mRNA targets as guides for the RNA-induced silencing complex (RISC). Both siRNAs and miRNAs are born double stranded. Surprisingly, loading these small RNA duplexes into Argonaute proteins, the core components of RISC, requires ATP, whereas separating the two small RNA strands within Argonaute does not. Here we show that the Hsc70/Hsp90 chaperone machinery is required to load small RNA duplexes into Argonaute proteins, but not for subsequent strand separation or target cleavage. We envision that the chaperone machinery uses ATP and mediates a conformational opening of Ago proteins so that they can receive bulky small RNA duplexes. Our data suggest that the chaperone machinery may serve as the driving force for the RISC assembly pathway.
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► Hsc70/Hsp90 machinery mediates ATP-dependent RISC loading of small RNA duplexes ► Hsc70/Hsp90 machinery is dispensable for duplex separation or target cleavage ► Hsc70-4 is an important factor for RISC loading in flies |
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AbstractList | Small silencing RNAs--small interfering RNAs (siRNAs) or microRNAs (miRNAs)--direct posttranscriptional gene silencing of their mRNA targets as guides for the RNA-induced silencing complex (RISC). Both siRNAs and miRNAs are born double stranded. Surprisingly, loading these small RNA duplexes into Argonaute proteins, the core components of RISC, requires ATP, whereas separating the two small RNA strands within Argonaute does not. Here we show that the Hsc70/Hsp90 chaperone machinery is required to load small RNA duplexes into Argonaute proteins, but not for subsequent strand separation or target cleavage. We envision that the chaperone machinery uses ATP and mediates a conformational opening of Ago proteins so that they can receive bulky small RNA duplexes. Our data suggest that the chaperone machinery may serve as the driving force for the RISC assembly pathway. Small silencing RNAs—small interfering RNAs (siRNAs) or microRNAs (miRNAs)—direct posttranscriptional gene silencing of their mRNA targets as guides for the RNA-induced silencing complex (RISC). Both siRNAs and miRNAs are born double stranded. Surprisingly, loading these small RNA duplexes into Argonaute proteins, the core components of RISC, requires ATP, whereas separating the two small RNA strands within Argonaute does not. Here we show that the Hsc70/Hsp90 chaperone machinery is required to load small RNA duplexes into Argonaute proteins, but not for subsequent strand separation or target cleavage. We envision that the chaperone machinery uses ATP and mediates a conformational opening of Ago proteins so that they can receive bulky small RNA duplexes. Our data suggest that the chaperone machinery may serve as the driving force for the RISC assembly pathway. [Display omitted] ► Hsc70/Hsp90 machinery mediates ATP-dependent RISC loading of small RNA duplexes ► Hsc70/Hsp90 machinery is dispensable for duplex separation or target cleavage ► Hsc70-4 is an important factor for RISC loading in flies |
Author | Yoda, Mayuko Kobayashi, Maki Sakaguchi, Yuriko Iwasaki, Shintaro Suzuki, Tsutomu Tomari, Yukihide Katsuma, Susumu |
Author_xml | – sequence: 1 givenname: Shintaro surname: Iwasaki fullname: Iwasaki, Shintaro organization: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan – sequence: 2 givenname: Maki surname: Kobayashi fullname: Kobayashi, Maki organization: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan – sequence: 3 givenname: Mayuko surname: Yoda fullname: Yoda, Mayuko organization: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan – sequence: 4 givenname: Yuriko surname: Sakaguchi fullname: Sakaguchi, Yuriko organization: Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan – sequence: 5 givenname: Susumu surname: Katsuma fullname: Katsuma, Susumu organization: Department of Agricultural and Environmental Biology, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan – sequence: 6 givenname: Tsutomu surname: Suzuki fullname: Suzuki, Tsutomu organization: Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan – sequence: 7 givenname: Yukihide surname: Tomari fullname: Tomari, Yukihide email: tomari@iam.u-tokyo.ac.jp organization: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20605501$$D View this record in MEDLINE/PubMed |
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Snippet | Small silencing RNAs—small interfering RNAs (siRNAs) or microRNAs (miRNAs)—direct posttranscriptional gene silencing of their mRNA targets as guides for the... Small silencing RNAs--small interfering RNAs (siRNAs) or microRNAs (miRNAs)--direct posttranscriptional gene silencing of their mRNA targets as guides for the... Small silencing RNAs - small interfering RNAs (siRNAs) or microRNAs (miRNAs) - direct posttranscriptional gene silencing of their mRNA targets as guides for... |
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SubjectTerms | Adenosine Triphosphate - metabolism Animals ATP Drosophila melanogaster Drosophila Proteins - genetics Drosophila Proteins - metabolism HSC70 Heat-Shock Proteins - genetics HSC70 Heat-Shock Proteins - metabolism HSP90 Heat-Shock Proteins - genetics HSP90 Heat-Shock Proteins - metabolism MicroRNAs - genetics MicroRNAs - metabolism PROTEINS RNA RNA, Double-Stranded - genetics RNA, Double-Stranded - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism RNA-Induced Silencing Complex - genetics RNA-Induced Silencing Complex - metabolism |
Title | Hsc70/Hsp90 Chaperone Machinery Mediates ATP-Dependent RISC Loading of Small RNA Duplexes |
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