Related Experiment Videos
The molecular mode of brain mRNA processing damage followed by the suppression of post-transcriptional poly(A)
1Laboratory of Toxicology, Moscow City Station for Sanitation and Epidemiology, USSR.
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 hn RNA (pre-mRNA) isolated from brain 80S hn RNP 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.
Insights
Cordycepin suppresses polyadenylation in rat brain mRNA precursors, causing degradation of translatable sequences in hnRNP particles. This impacts both poly(A)(+) and poly(A)- pre-mRNA, affecting RNA stability.
Area of Science:
- Molecular Biology
- Neuroscience
- RNA Biology
Background:
- Polyadenylation is crucial for mRNA stability and translation.
- Heterogeneous nuclear ribonucleoprotein particles (hnRNPs) package pre-mRNA in the nucleus.
- Cordycepin is a known inhibitor of polyadenylation.
Purpose of the Study:
- To investigate the effect of cordycepin-induced polyadenylation suppression on translatable pre-mRNA sequences within rat brain hnRNPs.
- To characterize changes in hnRNP particles lacking polyadenylation.
Main Methods:
- Comparative analysis of two-dimensional gel-electrophoretic mapping.
- In vitro translation using a reticulocyte cell-free system.
- Isolation and analysis of rapidly labeled 9-17S hn RNA (pre-mRNA) from rat brain hnRNP particles.
Main Results:
- Complete suppression of polyadenylation by cordycepin leads to degradation of translatable sequences in both poly(A)(+) and poly(A)- pre-mRNA within hnRNPs.
- Extended cordycepin exposure results in hnRNP particles devoid of poly(A)+ RNA and poly(A)-binding proteins.
- These altered hnRNP particles exhibit different RNA/protein ratios and reduced resistance to RNase activity.
Conclusions:
- Cordycepin-induced polyadenylation inhibition disrupts the integrity of translatable pre-mRNA within hnRNPs.
- The formation of abnormal hnRNP particles affects RNA stability and processing.
- Cordycepin does not directly inhibit nuclear poly(A)-binding protein biosynthesis within the experimental timeframe.