Structural Features of Myelin Basic Protein mRNAs Influence Their Translational Efficiencies

The myelin basic protein (MBP) gene expresses several alternatively spliced products with the same 5' and 3' untranslated regions (UTRs). It has been reported that its expression may be regulated not only at the transcriptional level but also at the translational level during development. We engineered several MBP mRNA deletion mutants with 5' (-48, -37, -27, -22, and -10) and 3' UTRs of differing lengths and examined the translational efficiencies of these constructs in cell-free systems. The translational efficiencies of the constructs differed significantly over a range of almost 10-fold. A deletion of 11 nucleotides from the 5' end of the natural (i.e., -48) MBP mRNA resulted in an approximate fourfold reduction in translational efficiency. Further truncation of the 5' UTR increased the translational efficiencies of the constructs as has been observed with many RNAs. These results suggest that there may be a positive control element between -48 and -37 nucleotides in the 5' UTR of MBP mRNA. The effects of modifying the lengths of the 5' UTR on the translational efficiency of mRNAs encoding the 21.5-kDa and 14-kDa MBPs were the same, suggesting that the effect observed was not unique to the 21.5-kDa MBP mRNA. Truncating the 3' UTR of four different alternatively spliced MBP mRNAs also altered their translational efficiencies. Thus, the 5' and 3' UTRs of MBP mRNAs appear to influence the translation of these mRNAs, and such factors may be involved in the translational regulation of MBP gene expression.