Model showing the non-templated functions of the 5’CL and cre hairpin during cre-dependent VPgpUpU synthesis. The model shows long-distance interaction between the 5’CL-RNP complex, formed with 3CDpro and PCBP, and the cre-RNP complex, formed with 3CDpro, 3Dpol and VPg. The interaction between the 5’CL-RNP complex and the cre-RNP complex results in the efficient synthesis of VPgpUpU by 3Dpol. For clarity, cellular membranes are not depicted and additional viral and cellular proteins that may be required are not shown in this model and in the other models in this review.