Asymmetry in the assembly of the RNAi enzyme complex
- Publication Type:
- Journal Article
- Citation:
- Cell, 2003, 115 (2), pp. 199 - 208
- Issue Date:
- 2003-10-17
Closed Access
Filename | Description | Size | |||
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2010003459OK.pdf | 661.9 kB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Schwarz, DS | en_US |
dc.contributor.author |
Hutvágner, G https://orcid.org/0000-0002-7231-9446 |
en_US |
dc.contributor.author | Du, T | en_US |
dc.contributor.author | Xu, Z | en_US |
dc.contributor.author | Aronin, N | en_US |
dc.contributor.author | Zamore, PD | en_US |
dc.date.issued | 2003-10-17 | en_US |
dc.identifier.citation | Cell, 2003, 115 (2), pp. 199 - 208 | en_US |
dc.identifier.issn | 0092-8674 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/14941 | |
dc.description.abstract | A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5′ ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis. | en_US |
dc.relation.ispartof | Cell | en_US |
dc.relation.isbasedon | 10.1016/S0092-8674(03)00759-1 | en_US |
dc.subject.classification | Developmental Biology | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Drosophila melanogaster | en_US |
dc.subject.mesh | RNA-Induced Silencing Complex | en_US |
dc.subject.mesh | Superoxide Dismutase | en_US |
dc.subject.mesh | RNA Helicases | en_US |
dc.subject.mesh | RNA, Antisense | en_US |
dc.subject.mesh | MicroRNAs | en_US |
dc.subject.mesh | RNA, Small Interfering | en_US |
dc.subject.mesh | RNA, Double-Stranded | en_US |
dc.subject.mesh | RNA, Messenger | en_US |
dc.subject.mesh | RNA, Untranslated | en_US |
dc.subject.mesh | Adenosine Diphosphate | en_US |
dc.subject.mesh | Adenosine Triphosphate | en_US |
dc.subject.mesh | RNA Interference | en_US |
dc.subject.mesh | Base Sequence | en_US |
dc.subject.mesh | Base Pairing | en_US |
dc.subject.mesh | Phosphorylation | en_US |
dc.subject.mesh | Kinetics | en_US |
dc.subject.mesh | Base Pair Mismatch | en_US |
dc.subject.mesh | Hydrogen Bonding | en_US |
dc.subject.mesh | Models, Biological | en_US |
dc.subject.mesh | Superoxide Dismutase-1 | en_US |
dc.title | Asymmetry in the assembly of the RNAi enzyme complex | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 2 | en_US |
utslib.citation.volume | 115 | en_US |
utslib.for | 0601 Biochemistry and Cell Biology | en_US |
utslib.for | 06 Biological Sciences | en_US |
utslib.for | 11 Medical and Health Sciences | en_US |
dc.location.activity | ISI:000186039200011 | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Engineering and Information Technology | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
utslib.copyright.status | closed_access | |
pubs.issue | 2 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 115 | en_US |
Abstract:
A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5′ ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis.
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