Secondary structure of mouse and rabbit alpha- and beta-globin mRNAs: differential accessibility of alpha and beta initiator AUG codons towards nucleases.

The nucleotide sequence from the 5' terminus inward of one third of mouse alpha- and beta maj-globin messenger RNAs has been established. In addition, using 5' 32P end-labeled mRNAs as substrates and S1 and T1 nucleases as probes for single-stranded regions, the secondary structures of mouse and rabbit alpha- and beta-globin mRNAs have been analyzed. Our results indicate that the AUG initiator codon in both mouse and rabbit beta-globin mRNA is quite susceptible to cleavage with S1 and T1 nucleases, suggesting that it resides in a single-stranded exposed region. In contrast, the initiator AUG in the alpha-globin mRNA of both species is inaccessible to cleavage, indicating that it is either buried by tertiary structure or is base-paired. Since the rate of initiation of protein synthesis with beta-globin mRNA in rabbit reticulocyte is 30--40% faster than for alpha-globin mRNA, these results imply a possible correlation between the differential rates of initiation with these two mRNAs and the accessibility of the respective AUG initiator codons.