Posttranscriptional Events in the Expression of Myelin Protein Genesa

Abstract

A number of posttranscriptional events may be involved in regulating the expression of the myelin protein genes. One such event in the expression of the myelin basic protein (MBP) gene is the translocation of MBP mRNAs from oligodendrocyte cell bodies to their processes. This translocation can be observed in vivo and in primary mixed glial cell cultures. In jimpy brains the translocation of MBP mRNA appears to be disrupted, so that most of the mRNA remains associated with cell bodies. This apparent failure of translocation may account for the lack of incorporation of newly synthesized MBP into jimpy myelin. In quaking myelin, where MBP assembly is also defective, translocation appears to be normal, suggesting that incorporation of MBP into the membrane also is regulated posttranslationally. We have identified a number of the structural features of MBP mRNAs that influence the efficiencies with which they are translated and may be involved in regulating the levels of individual MBP produced. We also found that glucocorticoids stimulate the translation of MBP and PLP mRNAs and inhibit the translation of CNP mRNA in cell-free systems. Our results suggest that this pattern of translational regulation may be physiologically meaningful, especially during maturation of myelin. The mechanism by which the steroids modulate translation of these messages appears to be novel. Analysis of the effect of steroids on cRNAs produced from engineered MBP cDNA constructs has permitted the identification of a nine nucleotide element involved in this steroid modulation within the 5' untranslated region of the MBP mRNA.