Computational insight into crucial interaction between Pcf11 and Ydh1 for pre-mRNA 3ˈ-end processing

Pre-mRNA processing in eukaryotes involves capping, splicing, cleavage, and polyadenylation. Various proteins regulating this key transcriptional event in humans share considerable homology with <i>Saccharomyces cerevisiae</i> proteins. Among these proteins, Pcf11 is a crucial component of the yeast CF IA sub-unit, and Ydh1 is part of the CPF sub-unit. Both these proteins have a significant role during the pre-mRNA processing of the nascent transcription. Our i<i>n silico</i> analysis highlights probable interaction between residues of Pcf11-Ydh1 and their role in mRNA processing events. These outcomes provide evidence for direct interaction between the domain from residues 116 to 204 of Pcf11 (Pcf11^116-204) with the N-terminal region of Ydh1 (residues 1-246; Ydh1^1-246). Molecular docking and MD simulations shed light on the structure and dynamics of the protein-protein complex that includes binding affinity and binding interface of Pcf11 and Ydh1 interaction. These outcomes would pave the way to further design <i>in vitro</i> and <i>in vivo</i> studies to determine the function of the Pcf11^116-204 domain, which has not been previously analyzed; this would also facilitate deciphering the crucial role of Ydh1 and Pcf11 in assembling the cleavage and polyadenylation complex for executing co-transcriptional processing to generate mature mRNA.