Peer-Reviewed Journal Details
Mandatory Fields
Ivanov, IP;Shin, BS;Loughran, G;Tzani, I;Young-Baird, SK;Cao, C;Atkins, JF;Dever, TE
2018
April
Molecular Cell
Polyamine Control of Translation Elongation Regulates Start Site Selection on Antizyme Inhibitor mRNA via Ribosome Queuing
Validated
WOS: 54 ()
Optional Fields
INTEGRATED STRESS-RESPONSE GENE-SPECIFIC TRANSLATION OPEN READING FRAMES ORNITHINE-DECARBOXYLASE EUKARYOTIC TRANSLATION MODULATES AUTOREGULATION SACCHAROMYCES-CEREVISIAE NUCLEOTIDE RESOLUTION PROMOTES TRANSLATION MAMMALIAN-CELLS
70
254
Translation initiation is typically restricted to AUG codons, and scanning eukaryotic ribosomes inefficiently recognize near-cognate codons. We show that queuing of scanning ribosomes behind a paused elongating ribosome promotes initiation at upstream weak start sites. Ribosomal profiling reveals polyamine-dependent pausing of elongating ribosomes on a conserved Pro-Pro-Trp (PPW) motif in an inhibitory non-AUG-initiated upstream conserved coding region (uCC) of the antizyme inhibitor 1 (AZIN1) mRNA, encoding a regulator of cellular polyamine synthesis. Mutation of the PPW motif impairs initiation at the uCC's upstream near-cognate AUU start site and derepresses AZIN1 synthesis, whereas substitution of alternate elongation pause sequences restores uCC translation. Impairing ribosome loading reduces uCC translation and paradoxically derepresses AZIN1 synthesis. Finally, we identify the translation factor eIF5A as a sensor and effector for polyamine control of uCC translation. We propose that stalling of elongating ribosomes triggers queuing of scanning ribosomes and promotes initiation by positioning a ribosome near the start codon.
CAMBRIDGE
1097-2765
10.1016/j.molcel.2018.03.015
Grant Details