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09:05
MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Molecular mechanism of target RNA transcript recognition by Argonaute-guide complexes
J S Parker1, S M Roe, D Barford
1Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.
Cold Spring Harbor Symposia on Quantitative Biology
|March 27, 2007
Summary
Structural analysis of archaeal Argonaute (AfPiwi) reveals its PIWI domain mechanism. It explains RNA-directed RNA endonuclease activity and microRNA seed region importance for target recognition.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Argonaute proteins are central to RNA-mediated gene silencing.
- Mechanisms of Argonaute proteins were poorly understood before structural studies.
Purpose of the Study:
- To elucidate the mechanism of Argonaute proteins through structural analysis.
- To investigate the PIWI domain of archaeal Argonaute homolog, AfPiwi.
Main Methods:
- Crystallographic analysis of the AfPiwi PIWI domain.
- RNA-AfPiwi binding assays.
- Biochemical and genetic data integration.
Main Results:
- The AfPiwi PIWI fold contains an RNase-H-like catalytic domain and a 5' RNA phosphate anchor site.
- AfPiwi binds RNA via a conserved carboxyl-terminal region and a novel metal-binding site.
- A structural model of Argonaute-siRNA complex explains RNA endonuclease specificity and miRNA seed function.
Conclusions:
- The study provides a structural basis for Argonaute's role in RNA-mediated gene silencing.
- Understanding AfPiwi mechanism offers insights into guide-target RNA recognition and specificity.
- The findings support the importance of the 5' RNA region for high-affinity interactions.
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