Translation initiation: What is the first ordered binding event at the ribosome during translation—the step that begins assembly of the initiation complex?

Introduction:
Translation begins with initiation, a carefully choreographed sequence that positions the start codon at the small ribosomal subunit. In bacteria, this involves the Shine–Dalgarno interaction; in eukaryotes, a 5′ cap–dependent scanning mechanism typically operates. The essence is that mRNA engages the small subunit before the large subunit joins to form a complete ribosome.

Given Data / Assumptions:

• Bacterial small subunit is 30S; eukaryotic is 40S.
• Initiation factors (IFs/eIFs) assist mRNA and initiator tRNA positioning.
• Large subunit (50S/60S) joins after correct start codon placement.

Concept / Approach:
The first ordered event is the recruitment of mRNA to the small subunit in the presence of initiation factors. In bacteria, base pairing between the Shine–Dalgarno sequence and 16S rRNA aligns AUG in the P site. In eukaryotes, the 43S preinitiation complex binds the mRNA cap and scans to the start codon. Only after start codon recognition does the large subunit associate, creating a functional 70S/80S ribosome ready for elongation.

Step-by-Step Solution:

Verification / Alternative check:
Toeprinting assays and ribosome profiling show mRNA engaging the small subunit early; antibiotics like kasugamycin that disrupt initiation support this ordering by preventing proper mRNA–30S interactions.

Why Other Options Are Wrong:

• Two subunits binding first: premature; assembly awaits correct mRNA positioning.
• mRNA to both subunits simultaneously: contradicted by initiation mechanisms.
• Initiator tRNA alone binding without mRNA: lacks start-codon guidance.
• Large subunit binding first: occurs only after start-codon recognition.

Common Pitfalls:
Assuming ribosomal subunits assemble before mRNA docking or conflating bacterial and eukaryotic details while missing the shared principle: mRNA–small subunit engagement occurs early.

Final Answer:
Binding of mRNA to the small ribosomal subunit (with initiation factors)