Post-transcriptional modification of globin RNA.

During the last three years, significant progress has been made in the characterization of the structure of globin RNA precursors and the steps involved in their modifications to mature mRNA. Aside from the coding sequence, IVSs in RNA precursors have a critical function in the formation of mature mRNA. However, certain questions regarding the role IVSs might have in RNA processing still need to be answered. In order to understand normal globin gene expression, it will be important to know whether specific nucleoside sequences or conformational changes in the structure of the RNA due to IVSs are required for each processing enzyme in the stepwise cleavage-ligation reaction. The availability of purified RNA processing intermediates for sequencing should enable us to map the cleavage-ligation sites in each RNA. It will be interesting to determine whether any methylated nucleotides exist in IVSs and whether methylation is involved in the processing pathway. In addition, further evidence should be forthcoming to demonstrate the importance of IVS removal in the transport of RNA from nucleus to cytoplasm. Information obtained from these studies should help us to understand further the post-transcriptional control of the globin gene expression in normal states as well as in states of abnormal globin chain synthesis, such as the thalassemias.