The CCR4-NOT complex is a large macromolecular assembly present both in the cytoplasm and the nucleus of eukaryotic cells and involved in a variety of distant processes related to expression of genetic information such as poly(A) tail shortening, transcription regulation, nuclear export and protein degradation. Herein we have performed a comprehensive structural characterization of the native CCR4-NOT complex from S. pombe. We have obtained a cryo-EM 3D recostruction of the complex which combined with different techniques such as immunomicroscopy, and RNA-nanogold labeling and the docking of the available high-resolution structures of different subunits and domains, have allowed us to propose for the first time the full molecular architecture of CCR4-NOT complex and to provide a mechanistic insight into the multifunctional properties of this complex.