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Posttranscriptional Regulation of Myelin Protein Gene Expression a
Author(s) -
CAMPAGI ANTHONY T.,
VERDI JOSEPH M.,
VERITY A. NEIL,
AMURUMARJEE SHASHI,
BYRAVAN SUJATHA
Publication year - 1991
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1991.tb15608.x
Subject(s) - gene expression , protein expression , gene , regulation of gene expression , myelin , microbiology and biotechnology , biology , genetics , chemistry , neuroscience , central nervous system
Regulation of myelin protein gene expression occurs at many different levels including transcription, mRNA translocation, translation, and posttranslational modification of myelin proteins prior to their assembly into the membrane. Translocation of myelin basic protein (MBP) mRNAs into oligodendrocyte processes was observed in vivo and in primary cultures, but no such translocation was observed for the mRNAs encoding the proteolipid protein (PLP) or myelin-associated glycoprotein. More than 99% of the mRNAs encoding 2'3'-cyclic nucleotide phosphodiesterase (CNP) remained associated with cell bodies. In the jimpy mutant, MBP mRNA translocation appeared to be impaired, but translocation occurred normally in quaking brains in vivo. We have found that steroids, such as glucocorticoids, stimulate the translation of MBP and PLP mRNAs in cell-free systems and inhibit the translation of CNP mRNA. This pattern of regulation is consistent with compositional changes noted in myelin during development. We have localized a nine nucleotide segment within the 5'-untranslated region of the MBP mRNA that is involved in the action of steroids on translation of this mRNA. We have also determined that the protein synthetic step modulated by the steroids is chain initiation, enhancing the rate at which new ribosomal subunits bind to the MBP mRNAs.