Understanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processes

Handle URI:
http://hdl.handle.net/10754/622347
Title:
Understanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processes
Authors:
Zhu, Lizhe; Jiang, Hanlun; Sheong, Fu Kit; Cui, Xuefeng; Wang, Yanli; Gao, Xin ( 0000-0002-7108-3574 ) ; Huang, Xuhui
Abstract:
At the core of RNA interference, the Argonaute proteins (Ago) load and utilize small guide nucleic acids to silence mRNAs or cleave foreign nucleic acids in a sequence specific manner. In recent years, based on extensive structural studies of Ago and its interaction with the nucleic acids, considerable progress has been made to reveal the dynamic aspects of various Ago-mediated processes. Here we review these novel insights into the guide-strand loading, duplex unwinding, and effects of seed mismatch, with a focus on two representative Agos, the human Ago 2 (hAgo2) and the bacterial Thermus thermophilus Ago (TtAgo). In particular, comprehensive molecular simulation studies revealed that although sharing similar overall structures, the two Agos have vastly different conformational landscapes and guide-strand loading mechanisms because of the distinct rigidity of their L1-PAZ hinge. Given the central role of the PAZ motions in regulating the exposure of the nucleic acid binding channel, these findings exemplify the importance of protein motions in distinguishing the overlapping, yet distinct, mechanisms of Ago-mediated processes in different organisms.
KAUST Department:
Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Zhu L, Jiang H, Sheong FK, Cui X, Wang Y, et al. (2016) Understanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processes. Progress in Biophysics and Molecular Biology. Available: http://dx.doi.org/10.1016/j.pbiomolbio.2016.09.008.
Publisher:
Elsevier BV
Journal:
Progress in Biophysics and Molecular Biology
KAUST Grant Number:
URF/1/1976-04
Issue Date:
5-Oct-2016
DOI:
10.1016/j.pbiomolbio.2016.09.008
Type:
Article
ISSN:
0079-6107
Sponsors:
This work was supported by the Hong Kong Research Grant Council [grant numbers HKUST C6009-15G, 16302214, 609813, AoE/M-09/12, M-HKUST601/13, and T13-607/12R to X.H.]; the National Science Foundation of China [grant number 21273188 to X.H.] and the King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) under Award No. URF/1/1976-04 to X.G.. This research made use of the resources of the Supercomputing Laboratory and computer clusters at King Abdullah University of Science & Technology (KAUST).
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0079610716300207
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorZhu, Lizheen
dc.contributor.authorJiang, Hanlunen
dc.contributor.authorSheong, Fu Kiten
dc.contributor.authorCui, Xuefengen
dc.contributor.authorWang, Yanlien
dc.contributor.authorGao, Xinen
dc.contributor.authorHuang, Xuhuien
dc.date.accessioned2017-01-02T09:08:27Z-
dc.date.available2017-01-02T09:08:27Z-
dc.date.issued2016-10-05en
dc.identifier.citationZhu L, Jiang H, Sheong FK, Cui X, Wang Y, et al. (2016) Understanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processes. Progress in Biophysics and Molecular Biology. Available: http://dx.doi.org/10.1016/j.pbiomolbio.2016.09.008.en
dc.identifier.issn0079-6107en
dc.identifier.doi10.1016/j.pbiomolbio.2016.09.008en
dc.identifier.urihttp://hdl.handle.net/10754/622347-
dc.description.abstractAt the core of RNA interference, the Argonaute proteins (Ago) load and utilize small guide nucleic acids to silence mRNAs or cleave foreign nucleic acids in a sequence specific manner. In recent years, based on extensive structural studies of Ago and its interaction with the nucleic acids, considerable progress has been made to reveal the dynamic aspects of various Ago-mediated processes. Here we review these novel insights into the guide-strand loading, duplex unwinding, and effects of seed mismatch, with a focus on two representative Agos, the human Ago 2 (hAgo2) and the bacterial Thermus thermophilus Ago (TtAgo). In particular, comprehensive molecular simulation studies revealed that although sharing similar overall structures, the two Agos have vastly different conformational landscapes and guide-strand loading mechanisms because of the distinct rigidity of their L1-PAZ hinge. Given the central role of the PAZ motions in regulating the exposure of the nucleic acid binding channel, these findings exemplify the importance of protein motions in distinguishing the overlapping, yet distinct, mechanisms of Ago-mediated processes in different organisms.en
dc.description.sponsorshipThis work was supported by the Hong Kong Research Grant Council [grant numbers HKUST C6009-15G, 16302214, 609813, AoE/M-09/12, M-HKUST601/13, and T13-607/12R to X.H.]; the National Science Foundation of China [grant number 21273188 to X.H.] and the King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) under Award No. URF/1/1976-04 to X.G.. This research made use of the resources of the Supercomputing Laboratory and computer clusters at King Abdullah University of Science & Technology (KAUST).en
dc.publisherElsevier BVen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0079610716300207en
dc.subjectArgonauteen
dc.subjectRNA interferenceen
dc.subjectMechanismen
dc.subjectKineticsen
dc.subjectProtein motionsen
dc.subjectMolecular dynamics simulationen
dc.subjectProtein-DNA/RNA dockingen
dc.subjectMarkov-state-modelsen
dc.subjectEnhanced samplingen
dc.titleUnderstanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processesen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalProgress in Biophysics and Molecular Biologyen
dc.contributor.institutionDepartment of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kongen
dc.contributor.institutionCenter of Systems Biology and Human Health, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kongen
dc.contributor.institutionBioengineering Graduate Program, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kongen
dc.contributor.institutionLaboratory of Non-Coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, Chinaen
kaust.authorCui, Xuefengen
kaust.authorGao, Xinen
kaust.grant.numberURF/1/1976-04en
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