RNA degradation paths in a 12-subunit nuclear exosome complex

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• The eukaryotic exosome is a vital multi-subunit complex responsible for RNA degradation, surveillance, and processing.
• The precise mechanisms by which the exosome achieves both complete RNA degradation and specific trimming of RNA substrates have remained unclear.

Purpose of the Study:

• To elucidate the structural basis for the dual RNA processing capabilities of the eukaryotic exosome.
• To understand how the exosome distinguishes between complete degradation and precise trimming of RNA.

Main Methods:

• Determined crystal structures of a yeast nuclear exosome complex (12 subunits) in association with various RNA molecules.
• Utilized a combination of structural and biochemical analyses to investigate RNA-exosome interactions.

Main Results:

• Revealed how single-stranded RNA can access the active sites of RNases Rrp44 or Rrp6 directly.
• Demonstrated RNA threading through the exosome's central channel towards the Rrp44 active site.
• Observed a conformational change (swinging mechanism) of the Rrp6-Rrp47 module when bulky RNA obstructs the channel entrance.

Conclusions:

• The exosome employs an RNA-dependent swinging mechanism involving its RNase subunits to coordinate processive degradation and partial trimming.
• This mechanism explains how a single molecular machine can perform distinct RNA processing outcomes based on RNA substrate characteristics.