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

Zhu, Lizhe; Jiang, Hanlun; Sheong, Fu Kit; Cui, Xuefeng; Wang, Yanli; Gao, Xin; Huang, Xuhui

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

Type

Article

Authors

Zhu, Lizhe

Jiang, Hanlun
Sheong, Fu Kit
Cui, Xuefeng
Wang, Yanli
Gao, Xin

Huang, Xuhui

KAUST Department

Computational Bioscience Research Center (CBRC)
Computer Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

KAUST Grant Number

URF/1/1976-04

Online Publication Date

2016-10-05

Print Publication Date

2017-09

Date

2016-10-05

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.

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.

Acknowledgements

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).