Carcinogenic aminoazo dyes in the liver disrupt the processing of newly synthesized nuclear RNA and its transport into the cytoplasm. Our previous experiments have shown that these disruptions are the result of the interference of the azocarcinogen with the function of the proteins of nuclear ribonucleoprotein particles. The goal of the proposed three-year project is: to isolate and characterize the proteins of these particles isolated from liver, and to identify changes in their properties and functions during the early stages of hepatocarcinogenesis. To identify the steps in RNA processing, which are blocked by azocarcinogen, different fractions of RNA (polysomal and non-polysomal cytoplasmic poly(A) plus and poly(A) minus RNA, nuclear poly(A) plus RNA, RNA bound to nuclear ribonucleoprotein particles) from livers of control animals and animals at different stages of azocarcinogenesis will be compared. The RNAs will be characterized by their complexity and the extent of secondary modifications. They will also be tested for the presence and distribution of sequences copied from repetitive DNA. The results of all analysis will be correlated. The function of individual proteins and the inhibition of this function by azocarcinogen will also be tested in an in vitro system. In this system we will try to reconstitute ribonucleoprotein particles fully active in RNA processing from proteins of normal and defective particles. The proposed experiments should identify azocarcinogen-induced changes in the protein population of nuclear ribonucleoprotein particles which lead to complete processing of nuclear RNA.
NIH ExPorter
NIH ExPorter