Messenger RNAs located in myelin sheath assembly sites

The targeting of mRNAs to specific subcellular locations is believed to fac ilitate the rapid and selective incorporation of their protein products int o complexes that may include membrane organelles. In oligodendrocytes, mRNA s that encode myelin basic protein (MBP) and select myelin-associated oligo dendrocytic basic proteins (MOBPs) locate in myelin sheath assembly sites ( MSAS). To identify additional mRNAs located in MSAS, we used a combination of subcellular fractionation and suppression subtractive hybridization. Mor e than 50% of the 1,080 cDNAs that were analyzed were derived from MBP or M OBP mRNAs, confirming that the method selected mRNAs enriched in MSAS. Of 9 0 other cDNAs identified, most represent one or more mRNAs enriched in rat brain myelin. Five cDNAs, which encode known proteins, were characterized f or mRNA size(s), enrichment in myelin, and tissue and developmental express ion patterns. Two of these, peptidylarginine deiminase and ferritin heavy c hain, have recognized roles in myelination. The corresponding mRNAs were of different sizes than the previously identified mRNA, and they had tissue a nd development expression patterns that were indistinguishable from those o f MBP mRNA. Three other cDNAs recognize mRNAs whose proteins (SH3p13, KIF1A , and dynein light intermediate chain) are involved in membrane biogenesis. Although enriched in myelin, the tissue and developmental distribution pat terns of these mRNAs differed from those of MBP mRNA. Six other cDNAs, whic h did not share significant sequence homology to known mRNAs, were also exa mined. The corresponding mRNAs were highly enriched in myelin, and four had tissue and developmental distribution patterns indistinguishable from thos e of MBP mRNA. These studies demonstrate that MSAS contain a diverse popula tion of mRNAs, whose locally synthesized proteins are placed to contribute to myelin sheath assembly and maintenance. Characterization of these mRNAs and proteins will help provide a comprehensive picture of myelin sheath ass embly.