Endogenous polybasic peptides cause slower movement of ribosomes but are not targets of the ribosome quality control complex (RQC)

Highly positively charged protein segments are known to result in poor translation efficiency by the action of the ribosome quality control complex (RQC). This effect may be explained by ribosome stalling caused by electrostatic interactions between the nascent peptide and the negatively charged ribosome exit tunnel. This leads to translation termination followed by activation of mRNA decay pathways and protein degradation by RQC. Polybasic peptides are mainly studied with reporter systems, where artificial sequences are introduced into heterologous genes. The unique example of an endogenous protein targeted by RQC is Rqc1, a protein essential for the RQC activity. RQC arguably regulates Rqc1 levels through a conserved polybasic domain present in its N-term. We aimed to check if RQC act as a regulatory mechanism for other endogenous proteins containing polybasic domains. Here we show by bioinformatics, ribosome profiling data, and western blot protein quantification that endogenous proteins containing polybasic domains similar to or even more positively charged than Rqc1 are not targeted by RQC, suggesting that endogenous polybasic domains are not sufficient to induce degradation by this complex. We further demonstrate that Rqc1 levels are not regulated by the RQC complex, but by Ltn1 alone, in a post-translational fashion.