Almost every eukaryotic mRNA has a 3’ polyA tail that contributes to post-transcriptional regulation of gene expression by regulating translation and mRNA stability. My laboratory studies the macromolecular protein complexes that control addition and removal of polyA tails: CPF, Ccr4–Not and Pan2–Pan3. We use a hybrid approach combining structural (cryo-EM, x-ray crystallography, NMR), biochemical, biophysical and genetic techniques to gain insights into their molecular mechanisms. I will discuss structural and mechanistic studies that have provided insights into the functions of these complexes. In addition, I will discuss recent advances in specimen preparation for electron cryo-microscopy (cryo-EM) that we are using to study these complexes.