Conserved Peptide Upstream Open Reading Frames Act Via Ribosome Stalling
to Regulate Translation in Response to Environmental Signals.
The regulation of protein synthesis plays a key role in growth and
development in all organisms. Upstream open reading frames (uORFs) are
commonly found in eukaryotic mRNA transcripts and typically inhibit
translation of downstream ORFs, in part by stalling ribosomes. Conserved
peptide uORFs (CPuORFs) are a rare subset of uORFs, some of which
conditionally regulate translation. Here we identify three Arabidopsis
CPuORFs that specifically regulate translation of any downstream ORF, in
response to the agriculturally significant environmental signals, heat
shock and water limitation. Mechanistically, we provide evidence that
CPuORF translation causes ribosome stalling, in a peptide
sequence-dependent manner, attenuating translation of downstream ORFs.
We propose a model in which plant CPuORFs are not simply on/off switches
for translation, but rather act conditionally, along a continuum, to
fine-tune translation dynamically.