The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells

Area of Science:

• Molecular Biology
• RNA Biology
• Cellular Mechanisms

Background:

• Aberrant mRNAs lacking termination codons are degraded by the non-stop decay (NSD) pathway in yeast.
• The yeast NSD pathway utilizes Ski7 to recognize and recruit the exosome for degradation.
• The existence and mechanism of NSD in mammalian cells remained unclear.

Purpose of the Study:

• To investigate the presence and mechanism of the non-stop decay pathway in mammalian cells.
• To identify the key protein factors involved in mammalian non-stop mRNA degradation.

Main Methods:

• Investigated mRNA degradation in a translation-dependent manner in mammalian cells.
• Utilized genetic and biochemical approaches to identify interacting protein complexes.
• Focused on the roles of eRF3 family members, Dom34, exosome-Ski complex, and listerin.

Main Results:

• Mammalian cells degrade unstable non-stop mRNA via a translation-dependent process.
• The pathway requires Hbs1 (an eRF3 family member), Dom34, and the exosome-Ski complex (Ski2/Mtr4, Dis3).
• Hbs1-Dom34 forms a complex with the exosome-Ski complex, and listerin is required for aberrant protein elimination.

Conclusions:

• The non-stop decay (NSD) pathway is conserved and functional in mammalian cells.
• Mammalian NSD involves Hbs1, Dom34, and the exosome-Ski complex, distinct from the yeast Ski7 mechanism.
• This study elucidates a crucial RNA surveillance mechanism in mammals.