Direct and indirect consequences of PAB1 deletion in the regulation of translation initiation, translation termination, and mRNA decay.

Many human diseases are caused by having too much or too little of certain cellular proteins. The amount of an individual protein is influenced by the level of its messenger mRNA (mRNA) and the efficiency of translation of the mRNA into a polypeptide chain by the ribosomes. Cytoplasmic poly(A)-binding protein (PABPC) plays numerous roles in the regulation of this multi-staged process, but understanding its specific role has been challenging because it is sometimes unclear whether experimental results are related to PABPC's direct role in a specific biochemical process or to indirect effects of its other roles, leading to conflicting models of PABPC's functions between studies. In this study, we characterized defects of each stage of protein synthesis in response to loss of PABPC in yeast cells by measuring whole-cell levels of mRNAs, ribosome-associated mRNAs, and proteins. We demonstrated that defects in most steps of protein synthesis other than the last can be explained by reduced levels of mRNAs that code for proteins important for that step in addition to loss of PABPC's direct role on that step. Our data and analyses serve as resources for the design of future studies of PABPC's functions.