INHIBITION OF TRANSLATION BY MESSENGER-RNA ENCODING NIPP-1, A NUCLEARINHIBITOR OF PROTEIN PHOSPHATASE-1

Transient transfection of COS-1 cells with an expression vector for NI PP-1, a nuclear subunit of protein phosphatase-1, did not result in an overexpression of NIPP-1 protein, although the levels of mRNA encodin g NIPP-1 increased dramatically. Moreover, high concentrations of NIPP -1 mRNA inhibited the translation in reticulocyte lysates of various u nrelated mRNAs. This inhibition of translation was caused by the NIPP- 1 messenger and not by the translation product, since mutation of the start codon abolished NIPP-1 protein production, but had no influence on the translational inhibition. Analysis of deletion mutants showed t hat the inhibition was mediated by a 0.5-kb fragment in the 5'-end of the NIPP-1 mRNA. This region, when inserted in the 5'-untranslated reg ion of the beta-galactosidase messenger, inhibited the translation of beta-galactosidase mRNA in COS-1 cells. A predicted highly stable seco ndary structure Delta G = -239.5 kJ/mol) is present between residues 3 00 and 500 of NIPP-1 mRNA. The possible importance of this structure i n the translational inhibition is discussed.