Possible Role of Poly A Sequences in Mammalian Cell mRNA

Possible Role of Poly (A) Sequences in Mammalian Cell mRNA 

The information above has demonstrated that many, if not most, mRNA s of animal cells contain poly (A) sequences. It has been shown that both HnRNA and polysomal mRNA contain poly (A) sequences (Lee et al, 1971 Edmonds et al, 1971 Darnell et al, 1971b Mendedd et al, 1972), Labeling kinetics of poly (A) containing RNA in HnRNA and polysomal mRNA suggest a precursor-product relationship between these two RNA populations and leads to the proposal that HnRNA can be converted to mRNA by the addition of a poly (A) sequence (Darnell et al, 1971b) that is, the poly(A) tract may be important for selecting HnRNA molecules for transport from the nucleus to the cytoplasm. 

Alkaline hydrolysates of mRNA from vaccinia virus (Kates, 1970) and mouse sarcoma 180 cells (Mendecki et al, 1972) show that the poly (A) tracts, 100-200 nucleotides in length, are located at the 3 -ter-minal end of the RNA molecules. Analysis of the reaction products of highly purified exoribonuclease specific for 3 -OH termini also indicates that most (and possibly all) of the poly (A) sequences are at the 3 -terminal end of the mRNA s (Molloy et al, 1972). This is supported by the fact that the time course of poly( A) labeling in polysomes indicates that this sequence is assembled after the rest of the RNA molecule has been completed (Mendecki et al, 1972). Poly (A) synthesis is sensitive to actinomycin D but to an extent less than that of the rest of the RNA molecule which further argues that the poly (A) segment is added after transcription is completed (Darnell et al, 1971b Mendecki et al, 1972). 

Penman et al (1970) noted that the drug cordycepin (3 -deoxyadeno-sine) has little effect on the incorporation of [ Hltiridine into HnRNA in HeLa cells, but causes a marked reduction in the appearance of mRNA in polysomes. It has been further shown that there is a marked reduction in the amount of labeled poly(A) in both HnRNA and polysomal mRNA after cordycepin treatment (Darnell et al, 1971b Mendecki et al., 1972). This suggests that cordycepin appears to affect primarily the enzyme processes concerned with the synthesis of poly (A) 

While the poly (A) sequences do seem to be involved in the transport of mRNA s from the nucleus, this does not seem to be the sole function of the poly (A) tract for example, adenovirus DNA appears to lack a DNA sequence complementary to poly (A) but replicates in the nucleus of the mammalian cell and appears to have a poly (A) tract added to the viral mRNA by host-cell mechanisms for transport of the adenovirus mRNA to the cytoplasm (Philipson et ah, 1971). As with cellular messages, cordycepin blocks both the labeling of the poly (A) tracts and the appearance of adenovirus-specific RNA in the cytoplasm of infected cells (Philipson et ah, 1971). In contrast, vaccinia virus replicates exclusively in the cytoplasm of cells it infects and still contains poly(A) sequences (Kates, 1970). Since no role in transport is involved here, it suggests that some mRNAs may require a poly (A) sequence for proper translation. Further, not all mammalian mRNAs contain poly (A) and still are transported to the cytoplasm for translation. Specifically, the 9 S histone message isolated by Adesnik and Darnell (1972) from HeLa cells lacks any detectable poly (A) sequence of any significant length. These workers have also shown that the exit time of the histone mRNA molecule from the nucleus is shorter than that of other messenger RNA s. 

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