AI Article Synopsis
- Bacteria utilize trans-translation and alternative factors ArfA and ArfB to remove stalled peptidyl-tRNA on ribosomes during protein synthesis.
- The eukaryotic protein ICT1 is similar to ArfB and shows equivalent activity in rescuing stalled ribosomes in lab tests.
- Both ArfB and ICT1 can rescue ribosomes with short mRNA stalls but not with longer mRNA extensions, indicating that ICT1 is crucial for ribosome rescue in human cells, highlighting its importance for cellular viability.
Article Abstract
Bacteria use trans-translation and the alternative rescue factors ArfA (P36675) and ArfB (Q9A8Y3) to hydrolyze peptidyl-tRNA on ribosomes that stall near the 3' end of an mRNA during protein synthesis. The eukaryotic protein ICT1 (Q14197) is homologous to ArfB. In vitro ribosome rescue assays of human ICT1 and Caulobacter crescentus ArfB showed that these proteins have the same activity and substrate specificity. Both ArfB and ICT1 hydrolyze peptidyl-tRNA on nonstop ribosomes or ribosomes stalled with ≤6 nucleotides extending past the A site, but are unable to hydrolyze peptidyl-tRNA when the mRNA extends ≥14 nucleotides past the A site. ICT1 provided sufficient ribosome rescue activity to support viability in C. crescentus cells that lacked both trans-translation and ArfB. Likewise, expression of ArfB protected human cells from death when ICT1 was silenced with siRNA. These data indicate that ArfB and ICT1 are functionally interchangeable, and demonstrate that ICT1 is a ribosome rescue factor. Because ICT1 is essential in human cells, these results suggest that ribosome rescue activity in mitochondria is required in humans.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814080 | PMC |
| http://dx.doi.org/10.1371/journal.pgen.1005964 | DOI Listing |
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