RNA channelling by the archaeal exosome

Area of Science:

• Structural Biology
• Molecular Biology
• Biochemistry

Background:

• Exosomes are vital molecular machines involved in RNA processing, decay, and quality control.
• Archaeal exosomes feature a unique nine-subunit structure with active (Rrp41) and inactive (Rrp42) RNase PH subunits, and an Rrp4/Csl4 subunit ring.

Purpose of the Study:

• To elucidate the high-resolution structure of the archaeal exosome from Sulfolobus solfataricus.
• To understand the mechanism of RNA binding and degradation by the archaeal exosome.

Main Methods:

• X-ray crystallography was employed to determine the structure of the archaeal exosome at 1.6 A resolution.
• A complex with a specifically designed RNA substrate was crystallized at 2.3 A resolution to visualize substrate binding.

Main Results:

• The crystal structure reveals the nine-subunit archaeal exosome complex.
• The RNA substrate binds at both the active site and within the central channel, interacting with multiple binding sites.
• Substrate entrapment in the central channel was observed.

Conclusions:

• The observed substrate binding and entrapment mechanisms explain the processive degradation of extended RNAs.
• The exosome's structure provides a basis for understanding its ability to stall structured RNAs, ensuring precise RNA processing.