Impacto da interrupção traducional no destino metabólico de polipeptídeos recém-sintetizados em Saccharomyces cerevisiae

Abstract

Translational arrest in eukaryotes promoted by mRNAs lacking stop-codons, or harboring rare codons, or those which undergo accidental cleavage, is capable of recruiting the RQC (Ribosome Quality Control) complex towards ribosomes. The RQC complex is responsible for the ubiquitination of the newly-synthesized, defective polypeptides, marking them for proteasomal degradation. In S. cerevisiae, the absence of the ubiquitin ligase E3 Ltn1p promotes the formation of protein aggregates from non-degraded defective polypeptides due to the activity of Tae2p. Using reporters that promote translational arrest, we observed that the aggregation of polypeptides synthesized from mRNAs containing rare codons requires the activity of Hel2p, a ribosome-associated protein. Interestingly, Hel2p also appears to be related to the degradation of newly-synthesized defective polypeptides from mRNAs that undergo accidental cleavage inside their coding region. In addition, we verified that the Rqc1p protein promotes high sensitivity to hygromycin B, an aminoglycoside that promotes translational frameshifting. Altogether, our data open the possibility of carrying out a more detailed study on the mechanisms of generation of protein aggregates as a result of translation defects, which may be related to neurodegenerative diseases