ATP-dependent human RISC assembly pathways.

Mayuko Yoda, Tomoko Kawamata, Zain Paroo, Xuecheng Ye, Shintaro Iwasaki, Qinghua Liu, Yukihide Tomari

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

Original languageEnglish (US)
Pages (from-to)17-23
Number of pages7
JournalNature structural & molecular biology
Volume17
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

RNA-Induced Silencing Complex
Argonaute Proteins
Adenosine Triphosphate
RNA
Gene Silencing
Drosophila melanogaster
MicroRNAs
Diptera
Small Interfering RNA
Seeds

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yoda, M., Kawamata, T., Paroo, Z., Ye, X., Iwasaki, S., Liu, Q., & Tomari, Y. (2010). ATP-dependent human RISC assembly pathways. Nature structural & molecular biology, 17(1), 17-23. https://doi.org/10.1038/nsmb.1733

ATP-dependent human RISC assembly pathways. / Yoda, Mayuko; Kawamata, Tomoko; Paroo, Zain; Ye, Xuecheng; Iwasaki, Shintaro; Liu, Qinghua; Tomari, Yukihide.

In: Nature structural & molecular biology, Vol. 17, No. 1, 01.2010, p. 17-23.

Research output: Contribution to journalArticle

Yoda, M, Kawamata, T, Paroo, Z, Ye, X, Iwasaki, S, Liu, Q & Tomari, Y 2010, 'ATP-dependent human RISC assembly pathways.', Nature structural & molecular biology, vol. 17, no. 1, pp. 17-23. https://doi.org/10.1038/nsmb.1733
Yoda, Mayuko ; Kawamata, Tomoko ; Paroo, Zain ; Ye, Xuecheng ; Iwasaki, Shintaro ; Liu, Qinghua ; Tomari, Yukihide. / ATP-dependent human RISC assembly pathways. In: Nature structural & molecular biology. 2010 ; Vol. 17, No. 1. pp. 17-23.
@article{d0c0723f55ab4d3983eea330b208e3d7,
title = "ATP-dependent human RISC assembly pathways.",
abstract = "The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.",
author = "Mayuko Yoda and Tomoko Kawamata and Zain Paroo and Xuecheng Ye and Shintaro Iwasaki and Qinghua Liu and Yukihide Tomari",
year = "2010",
month = "1",
doi = "10.1038/nsmb.1733",
language = "English (US)",
volume = "17",
pages = "17--23",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - ATP-dependent human RISC assembly pathways.

AU - Yoda, Mayuko

AU - Kawamata, Tomoko

AU - Paroo, Zain

AU - Ye, Xuecheng

AU - Iwasaki, Shintaro

AU - Liu, Qinghua

AU - Tomari, Yukihide

PY - 2010/1

Y1 - 2010/1

N2 - The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

AB - The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

UR - http://www.scopus.com/inward/record.url?scp=77449128456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77449128456&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1733

DO - 10.1038/nsmb.1733

M3 - Article

VL - 17

SP - 17

EP - 23

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 1

ER -