EMD-10181
Rabbit 80S ribosome stalled on a poly(A) tail
EMD-10181
Single-particle2.8 Å
Deposition: 03/08/2019
Map released: 04/12/2019
Last modified: 30/03/2022
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
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
(2019) Nat Struct Mol Biol , 26 , 1132 - 1140
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.
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.