Molecular mechanism of processive 3′ to 5′ RNA translocation in the active subunit of the RNA exosome complex. Recent experimental studies revealed structural details of 3′ to 5′ degradation of RNA molecules, performed byt he exosome complex. ssRNA is channeled through its multisubunit ring-like core into the active site tunnel of its key exonuclease subunit Rrp44, which acts both as an enzyme and a motor. Even in isolation, Rrp44 can pull and sequentially cleave RNA nucleotides, one at a time, without any external energy input and release a final 3−5 nucleotide long product. Using molecular dynamics simulations, we identify the main factors that control these processes. Our free energy calculations reveal that RNA transfer from solution into the active site of Rrp44 is highly favorable, but dependent on the length of the RNA strand. While RNA strands formed by 5 nucleotides or more correspond to a decreasing free energy along the translocation coordinate toward the cleavage site, a 4-nucleotide RNA experiences a free energy barrier along the same direction, potentially leading to incomplete cleavage of ssRNA and the release of short (3−5) nucleotide products. We provide new insight into how Rrp44 catalyzes a localized enzymatic reaction and performs an action distributed over several RNA nucleotides, leading eventually to the translocation of whole RNA segments into the position suitable for cleavage. Journal of the American Chemical Society., 2016.

Recent publications

Bignon, E.; Gattuso, H.; Morell, C.; Dehez, F.; Georgakilas, A. G.; Monari, A. & Dumont, E.
Correlation of bistranded clustered abasic DNA lesion processing with structural and dynamic DNA helix distortion.
Nucleic Acids Res.

2016,  (44), 8588-8599.

Wang, S.; Zhao, T.; Shao, X.; Chipot, C.; Cai, W.
Complex movements in rotaxanes: Shuttling coupled with conformational transition of cyclodextrins
J. Phys. Chem. C

2016,  (120), 19479-19486.

Gattuso, H.; Durand, E.; Bignon, E.; Morell, C.; Georgakilas, A. G.; Dumont, E.; Chipot, C.; Dehez, F.; Monari, A.
Repair rate of clustered abasic DNA lesions by human endonuclease: Molecular bases of sequence specificity
J. Phys. Chem. Lett

2016,  (19), 3760-3765.


- Renewal of the Laboratoire International Associé CNRS-University of Illinois at Urbana-Champaign on November 2016
- An update of ParseFEP is available in the latest version of VMD.
- 新的分子动力学讲义 (Dissemination).


Laboratoire International Associé
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