Translation elongation rate is regulated to ensure proper conformation and biological function of proteins, and its perturbation induces co-translational degradation of the arrested protein product by the proteasome, a process that is referred to as Ribosome Quality Control (RQC). We have demonstrated that the synthesis of poly-lysine by translation of the poly(A) sequence leads to translation arrest, and the level of the product of nonstop mRNA was reduced 100-fold by rapid mRNA degradation, translation repression and protein destabilization by the proteasome. Translation arrest during elongation step also leads to No-Go Decay (NGD), an endonucleolytic cleavage of the mRNA in the vicinity of the stalled ribosome. The mRNA fragments produced by the endonucleolytic cleavage, with free 3' or 5' termini, are further degraded by exosomes or by Xrn1 respectively. Ribosome stalling by functionally defective rRNAs is eliminated by 18S nonfunctional rRNA decay (18S NRD); however, the mechanisms by which stalled ribosomes induce these quality control systems are poorly understood. Here, we report that the Hel2 E3 ubiquitin ligase together its E2 ubiquitin-conjugating enzyme Ubc4 are involved in the NGD and RQC during synthesis of polybasic sequences. The Hel2-mediated ubiquitylations of ribosomal protein induces dissociation of the 80S ribosomes prior to functioning of Ltn1, another ubiquitin ligase involved in the RQC. Furthermore, we find that Hel2 is also required for 18S NRD and ubiquitylates of ribosomal protein for proteasomal degradation of non-functional 40S ribosomes. Based on these findings, we propose that Hel2 serves as a master regulator, termed ribosome-quality trigger factor 1, that senses and facilitates the stalled ribosomes for the quality control systems by ubiquitylating specific ribosomal components upon translational crises.