POSSIBLE MECHANISMS TO EXPLAIN CELLULAR PROTEIN SYNTHESIS INHIBITION

POSSIBLE MECHANISMS TO EXPLAIN CELLULAR PROTEIN SYNTHESIS INHIBITION 

The decrease in cellular protein synthesis could result from degradation or inactivation of cellular mRNA. Early studies (19 20), however, showed that cellular mRNA present in polysomes from poliovirus infected HeLa cells had the same sedimentation characteristics as that from uninfected cells. Because no appreciable degradation of cellular mRNA was observed, it was concluded that cellular protein synthesis inhibition does not result from an appreciable increase in endonuclease activity which would degrade cellular mRNA. 

The finding that most eukaryotic mRNAs have a poly(A) sequence at their 3 -terminus (See ref. 25 for a review) simplified the isolation procedure of mRNA considerably, since it could be bound to poly (u) or oligo dT embedded into filters or columns and recovered free of non-poly (A)-containing RNA such as rRNA. Using this technique the fate of pre-labeled cellular poly(A)-containing polysomal mRNA could easily be followed in uninfected and mengovirus infected L-cells (9). The pre-labeled cellular mRNA was found to associate with polysomes for up to at least 5 hours after infection, even though by this time there was considerable inhibition of cellular protein synthesis (Table 1). 

Expt Time after adsorpti on Poly(A)counts/mi n associated with polysomes (%)  

Purther evidence that cellular mRNA is not degraded after infection came from experiments using cellular mRNA extracted from infected cells to prime protein synthesis in extracts. From mouse plasmacytoma tumor cells Lawrence and Thach (26) isolated a poly(A)-containing 10S RNA fraction which in extracts was translated into a protein found in plasmacytoma cells, as determined by co-electrophoresis and tryptic mapping. This messenger RNA, when isolated from infected cells, was less active in translation than when isolated from uninfected cells by about However, mRNA 

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II. POSSIBLE MECHANISMS TO EXPLAIN CELLULAR PROTEIN SYNTHESIS INHIBITION... 

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