PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA

Summary
Organism
Homo sapiens (human)
Reactome
R-HSA-9954714
PubChem
R-HSA-9954714
Description
  • Non-stop mRNAs (mRNAs that lack a stop codon) result in ribosomal stalls proximal to the 3' end of the mRNA, which are resolved by a distinct pathway. In this case, a complex comprising PELO, a paralog of the ribosome release factor eRF1, and HBS1L:GTP, a paralog of the ribosome release factor eRF3:GTP, binds the stalled ribosome near the subunit interface and the mRNA entry site (Shao et al. 2013, and inferred from human PELO:HBS1L and rabbit ribosomes in Pisareva et al. 2011, inferred from yeast homologs DOM34:HBS1 in Shoemaker et al. 2010, Tsuboi et al. 2012, Guydosh and Green 2014, reviewed in Franckenberg et al. 2012). PELO:HBS1L preferentially acts on ribosomes that are bound to mRNAs that have fewer than 12 nucleotides extending 3' of the ribosomal P site (Pisareva et al. 2011).
    HBS1L hydrolyzes GTP and dissociates from PELO and the ribosome, exposing a site on PELO to which ABCE1 binds. ABCE1 then hydrolyzes ATP to cause a conformational change that splits the ribosome into 40S and 60S subunits (Shao et al. 2013, Shao and Hegde 2014, and inferred from the yeast homologs DOM34:HBS1 and archaeal homologs in Becker et al. 2012, inferred from the yeast homologs in Saito et al. 2013). ABCE1 and possibly the mRNA remain bound to the 40S ribosomal subunit, while the peptidyl-tRNA remains bound to the 60S ribosomal subunit as in the ASCC-mediated rescue pathway (Becker et al. 2012, reviewed in Franckenberg et al. 2012).
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Acknowledgements

Supported by JST NBDC Grant Number JPMJND2204

Partly supported by NIH Common Fund Grant #1U01GM125267-01


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