EMD-10181

Single-particle
2.8 Å
EMD-10181 Deposition: 03/08/2019
Map released: 04/12/2019
Last modified: 30/03/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-10181

Rabbit 80S ribosome stalled on a poly(A) tail

EMD-10181

Single-particle
2.8 Å
EMD-10181 Deposition: 03/08/2019
Map released: 04/12/2019
Last modified: 30/03/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Oryctolagus cuniculus, Homo sapiens
Sample: Rabbit 80S ribosome stalled on polyA mRNA
Fitted models: 6sgc (Avg. Q-score: 0.575)

Deposition Authors: Chandrasekaran V , Juszkiewicz S , Choi J , Puglisi JD , Brown A , Shao S , Ramakrishnan V , Hegde RS
Mechanism of ribosome stalling during translation of a poly(A) tail.
Chandrasekaran V , Juszkiewicz S , Choi J , Puglisi JD , Brown A , Shao S , Ramakrishnan V , Hegde RS
(2019) Nat Struct Mol Biol , 26 , 1132 - 1140
PUBMED: 31768042
DOI: doi:10.1038/s41594-019-0331-x
ISSN: 1545-9985
Abstract:
Faulty or damaged messenger RNAs are detected by the cell when translating ribosomes stall during elongation and trigger pathways of mRNA decay, nascent protein degradation and ribosome recycling. The most common mRNA defect in eukaryotes is probably inappropriate polyadenylation at near-cognate sites within the coding region. How ribosomes stall selectively when they encounter poly(A) is unclear. Here, we use biochemical and structural approaches in mammalian systems to show that poly-lysine, encoded by poly(A), favors a peptidyl-transfer RNA conformation suboptimal for peptide bond formation. This conformation partially slows elongation, permitting poly(A) mRNA in the ribosome's decoding center to adopt a ribosomal RNA-stabilized single-stranded helix. The reconfigured decoding center clashes with incoming aminoacyl-tRNA, thereby precluding elongation. Thus, coincidence detection of poly-lysine in the exit tunnel and poly(A) in the decoding center allows ribosomes to detect aberrant mRNAs selectively, stall elongation and trigger downstream quality control pathways essential for cellular homeostasis.