Control of transcription and translation by low molecular weight peptides (deprimerones) from chromatin and poly(A)-messenger RNA. Implication in the mechanism of carcinogenesis

Abstract

Poly(A)-mRNA isolated by phenol/chloroform extraction of rat liver polysomes, subtilism digestion, and poly(U)-Sepharose chromatography, contains a low molecular weight (approx. 1000) peptidic fraction. The peptides were extracted from a poly(A)-mRNA fraction by treatment with 80% ethanol; after ethanol evaporation they were purified on a Sephadex G-25 column and high-performance liquid chromatography on muBondapak C18. The isolated peptides were analyzed by cellulose gel thin-layer chromatography, high-pressure liquid chromatography and their amino acid composition was determined. They were compared with a chromatin peptidic fraction isolated from calf thymus nucleic by affinity chromatography on DNA-cellulose or on Sephadex G-25 column. Both groups of peptides from chromatin and from poly(A)-mRNA bind to the purified DNA thereby increasing its melting point; they significantly inhibit DNA transcription and RNA translation in reconstituted cell-free, peptide-free systems. It is suggested that these peptides are endogenous natural regulatory substances controlling gene expression in eucaryotic cells. We propose to name these regulatory peptides 'deprimerones' (from Latin 'deprimere') and describe various fractions of them as chromatin deprimerones, messenger deprimerones, gene deprimerones (for specific genes). Loss or decreased level of these deprimerones during the promotion of carcinogenesis is responsible for uncontrolled gene expression observed in cancer.