The cellular response to stress is coupled to an array of dynamic events. In response to DNA damaging stresses; DNA repair proteins move to sites of damage, the transcription machinery is modified, RNAs are organized into stress granules and P-bodies and proteins can be sequestered in aggregates. These dynamic changes collaborate to repair DNA, and alter the transcriptome and proteome to enable stress recovery. We identified an unexpected relocalization of the splicing factor Hsh155 to both intranuclear (INQ) and cytoplasmic (CytoQ) sites of protein quality control (PQC) upon exposure to the genotoxin methyl methanesulfonate (MMS). Hsh155 localization to PQC sites is promoted by molecular chaperones Hsp42 and Btn2 and is suppressed by the action of the Hsp104 disaggregase and the INQ component Apj1. Hsh155 protein is stable after MMS treatment and, like other aggregates, new translation is required for Hsh155 relocalization. Functionally, Hsh155 localization to PQC sites is correlated with a precipitous drop in splicing efficiency. To extend previous microarray studies, we conducted whole proteome analysis after MMS treatment and observed specific depletion of ribosomal proteins, whose mRNA products together command the largest need for spliceosomal function in yeast. We propose a model in which sequestration of Hsh155 is required to regulate splicing activity when ribosomal protein gene synthesis is arrested by genotoxic stress. These analyses reveal a novel function of PQC structures and highlight protein sequestration as a potential tool in the dynamic cellular control of the transcriptome and proteome under stress.