eIF2D promotes 40S ribosomal subunit recycling during intrinsic ribosome destabilization

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Eukaryotic initiation factor 2D (eIF2D) is known to be involved in translation initiation, reinitiation, and ribosome recycling.
• The exact function of eIF2D in these processes, particularly ribosome recycling, is not fully understood.

Purpose of the Study:

• To elucidate the precise role of eIF2D in ribosome recycling.
• To investigate the mechanism by which eIF2D functions during intrinsic ribosome destabilization (IRD).

Main Methods:

• Selective translation complex profiling (TCP-seq) was employed to map eIF2D association with mRNA.
• Cellular assays were used to assess ribosome accumulation and protein expression in eIF2D-deficient cells.

Main Results:

• eIF2D actively promotes 40S ribosome recycling during IRD, a process triggered by translating acidic amino acid sequences.
• eIF2D deficiency leads to the accumulation of unrecycled 40S subunits and subsequent 80S ribosome stalling.
• eIF2D preferentially binds to IRD-prone mRNA regions, and its unique winged helix domain facilitates 40S subunit binding.

Conclusions:

• eIF2D plays a critical role in 40S ribosome recycling, specifically during IRD.
• The study clarifies the distinct mechanism of eIF2D compared to the MCTS1-DENR complex.
• Loss of eIF2D function impacts the expression of proteins involved in processes like mRNA splicing.