Regulation of mammalian ribonucleotide reductase Ri mRNA stability is mediated by a ribonucleotide reductase Ri mRNA 3 ' - untranslated region cis - trans interaction through a protein kinase C - controlled pathway

Ribonucleotide reductase catalyses the reaction that eventually provides the four deoxyribonucleotides required for the synthesis and repair of DNA. U.v.-cross-linking and band-shift experiments have identified in COS 7 monkey cells an approx. 57 kDa ribonucleotide reductase RI mRNA-binding protein called RlBP, which binds specifically to a 49-nt region of the RI mRNA 3'-untranslated region (3'UTR). The RlBP-RNA binding activity was down-regulated by the tumour promoters phorbol 12-myristate 13-acetate (PMA; 'TPA') and okadaic acid, and up-regulated by the protein kinase C inhibitor staurosporine, in a dose-dependent fashion. Furthermore, staurosporine treatment decreased the stability of Rl and CAT (chloramphenicol acetyltransferase)/Rl hybrid mRNAs, where-