Adequate regulation of gene expression is essential to ensure the health, fitness, and development of all living organisms. While transcription is the primary focus of regulation, post-transcriptional control also plays a crucial role. The Ccr4-Not complex is a conserved, multi-subunit complex found in all eukaryotes. It plays a pivotal role in mRNA metabolism from inception to degradation. This complex is present in both the nucleus and the cytoplasm, making it ideal for linking transcription and translation, thus sitting at the core of eukaryotic gene expression circuitry. In the nucleus, the Ccr4-Not complex associates with the transcription machinery, factors that prepare mRNA for export to the cytoplasm, and components of nuclear quality control. In the cytoplasm, it is found in translating ribosomes and RNA granules, thereby influencing the stability and translatability of mRNAs. It plays a significant role during translation in both translational and co-translational processes, and it also protects stalled ribosomes from quality control mechanisms. The complex exhibits two enzymatic activities: deadenylation, which removes the polyadenylated tails of mRNAs, and ubiquitin ligation, which attaches ubiquitin molecules to protein targets for either degradation or functional modification. Several studies have revealed the roles of the complex, particularly of the Not-subunits, that are not linked to deadenylation but are relevant for translation. This study examines the potential roles of the nuclear Not1 and Not4, two subunits of the Ccr4-Not complex, in the context of the idea of mRNA imprinting and investigates how nuclear forms of the proteins impact their downstream regulation in the cytoplasm. The findings provide new insights into the dual roles of the complex in the nucleus and cytoplasm while also validating some previous discoveries made by former lab members.