The Rrp4–exosome complex recruits and channels substrate RNA by a unique mechanism

5 years ago

The Rrp4–exosome complex recruits and channels substrate RNA by a unique mechanism

Maxime J Audin, Jan Philip Wurm, Remco Sprangers, Milos A Cvetkovic, Stefan Schütz

The exosome is a large molecular machine involved in RNA degradation and processing. Here we address how the trimeric Rrp4 cap enhances the activity of the archaeal enzyme complex. Using methyl-TROSY NMR methods we identified a 50-Å long RNA binding path on each Rrp4 protomer. We show that the Rrp4 cap can thus simultaneously recruit three substrates, one of which is degraded in the core while the others are positioned for subsequent degradation rounds. The local interaction energy between the substrate and the Rrp4–exosome increases from the periphery of the complex toward the active sites. Notably, the intrinsic interaction strength between the cap and the substrate is weakened as soon as substrates enter the catalytic barrel, which provides a means to reduce friction during substrate movements toward the active sites. Our data thus reveal a sophisticated exosome–substrate interaction mechanism that enables efficient RNA degradation.

Publisher URL: http://dx.doi.org/10.1038/nchembio.2328

DOI: 10.1038/nchembio.2328