The Molecular Mode of Brain Mrna Processing Damage Followed by the Suppression of Post-Transcriptional Poly(A) Synthesis with Cordycepin

Abstract

Complete suppression of polyadenylation of nuclear precursors of rat brain mRNA by cordycepin leads to degradation of some translatable sequences of both poly(A)⁺ - and poly(A)⁻ pre-mRNA localized in 80S hnRNP-particles. This fact has been established by comparative analysis of the data of two-dimensional gel-electrophoretic mapping of translation products synthesized in reticulocytic cell-free system using the exogenous purified templates of rapidly labelling translatable 9-17S hnRNA (pre-mRNA) isolated from brain 80S hnRNP particles of experimental (4 hrs after cordycepin injection) and control (injection of physiological solution) adult healthy male rats. Long contact of brain cells with cordycepin (4 or more hrs) creates conditions for formation of hnRNP-particles devoid of poly(A)⁺ RNA and poly(A)-binding proteins. These particles differ from “normal” ones by the value of the RNA/protein ratio, and by considerably lower resistance to the action of exogenous ribonucleases and endogenous RNase. Cordycepin does not have a direct effect on biosynthesis of nuclear poly(A)-binding proteins within the duration of the experiment (8 hrs). The phenomena described are discussed.

Key Words:

• cordycepin (3′-deoxyadenosine)
• brain nuclear pre-mRNA processing
• poly (A)