The messenger RNA precursors (pre-mRNA) 3-end processing occurs in a two-step co-transcriptional coupled reaction, denoted as cleavage and polyadenylation. Both processes depend on trans-acting factors interacting in a coordinated manner with cis-sequence motifs located at the 3 untranslated region of transcripts. In this paper, we reviewed mechanisms involved in pre-mRNA processing in eukaryotic organisms, including our own findings about sequences and proteins potentially involved in mRNA 3-end formation in the protozoan parasite Entamoeba histolytica. Interestingly, protein sequence comparisons among E. histolytica, yeast, and human pre-mRNA processing machineries showed that amoeba pre-mRNA 3-end processing machinery appears to be in an intermediate evolutionary position between mammals and yeast. In addition, the presence of non canonical poly(A) polymerases family recently identified in E. histolytica, adds more complexity to the mRNA 3-end formation process in this ancient eukaryote.