The cleavage and polyadenylation step are indispensable for pre-mRNA processing in eukaryotes. Defective 3'- end maturation of precursor mRNA has catastrophic effects, leading to several diseases in humans. This processing is orchestrated by a complex machinery comprising more than 20 proteins in Saccharomyces cerevisiae. Endonucleolytic cleavage followed by the addition of poly(A) tail at the 3'-end of the precursor mRNA requires CPF, CF IA and CF IB proteins. Clp1, a protein factor of the CF IA sub-unit is indispensable for the functioning of this machinery. Based on in silico analysis including molecular docking via different docking servers and molecular dynamics (MD) simulations, the current study provides key evidence of the Clp1 N-terminal (1-100 amino acids) domain's interaction with Ssu72. MD simulations consolidate this binding between Clp1 and Ssu72. Our study presents strong evidence of a model where Clp1 (CF IA) associates with Ssu72 (CPF) and both the proteins are vital for tethering the complex for mediating cleavage and polyadenylation reaction during the key events of pre-mRNA 3'-end processing. These findings may pave the way to decipher the individual roles of Clp1 and Ssu72 during pre-mRNA maturation.

• PMID: 39522172
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Journal Article

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Kaur M, Agrawal P, Singh G, Kumar GS, Barnwal RP

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