What is a uORF (upstream open reading frame) and how does it regulate translation?

• A. A uORF in the 5' UTR can divert ribosomes, reducing translation of the main coding sequence.
• B. A uORF is a coding region in downstream region after main ORF.
• C. uORF increases ribosome traffic to main ORF.
• D. uORF affects mRNA splicing.

Answer: (A)

A uORF sits in the 5' untranslated region and influences where the ribosome starts translating. When the ribosome attaches to the mRNA and scans to find a start codon, it may encounter a uORF start codon and begin translating that short upstream ORF. After finishing the uORF, the ribosome often dissociates, or if it reinitiates, it does so with lower efficiency at the main coding sequence. Because many ribosomes are diverted or lose the chance to start at the main AUG, the overall translation of the primary protein is reduced. Some systems can allow limited reinitiation, but the general outcome is downregulation of the main ORF translation due to this upstream initiation event. That’s why this option best describes how a uORF regulates translation.

The other ideas don’t fit: a uORF is not a downstream coding region after the main ORF, so it wouldn’t be labeled as upstream if it were downstream. It does not typically increase ribosome traffic to the main ORF; it usually competes for the scanning ribosomes. And it is not a mechanism of altering mRNA splicing.