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© The Rockefeller University Press, 0021-9525/1997//1077 $5.00
The Journal of Cell Biology, Volume 138, Number 5, , 1997 1077-1087


Article

Transport and Localization Elements in Myelin Basic Protein mRNA



Kevin Ainger*, Daniela Avossa*, Amy S. Diana*, Christopher Barry{ddagger}, Elisa Barbarese{ddagger}, and John H. Carson*

* Department of Biochemistry, and {ddagger} Department of Neurology, University of Connecticut Health Center, Farmington, Connecticut 06030

Myelin basic protein (MBP) mRNA is localized to myelin produced by oligodendrocytes of the central nervous system. MBP mRNA microinjected into oligodendrocytes in primary culture is assembled into granules in the perikaryon, transported along the processes, and localized to the myelin compartment. In this work, microinjection of various deleted and chimeric RNAs was used to delineate regions in MBP mRNA that are required for transport and localization in oligodendrocytes. The results indicate that transport requires a 21-nucleotide sequence, termed the RNA transport signal (RTS), in the 3' UTR of MBP mRNA. Homologous sequences are present in several other localized mRNAs, suggesting that the RTS represents a general transport signal in a variety of different cell types. Insertion of the RTS from MBP mRNA into nontransported mRNAs, causes the RNA to be transported to the oligodendrocyte processes. Localization of mRNA to the myelin compartment requires an additional element, termed the RNA localization region (RLR), contained between nucleotide 1,130 and 1,473 in the 3' UTR of MBP mRNA. Computer analysis predicts that this region contains a stable secondary structure. If the coding region of the mRNA is deleted, the RLR is no longer required for localization, and the region between nucleotide 667 and 953, containing the RTS, is sufficient for both RNA transport and localization. Thus, localization of coding RNA is RLR dependent, and localization of noncoding RNA is RLR independent, suggesting that they are localized by different pathways.


Abbreviations used in this paper: ER, endoplasmic reticulum; GFP, green fluorescent protein; MAP, microtubule-associated protein; MBP, myelin basic protein; PLP, proteolipid protein; RLR, RNA localization region; RTS, RNA transport sequence; SRP, signal recognition particle; UTR, untranslated region.

K. Ainger and D. Avossa contributed equally to this work.

Please address all correspondence to John H. Carson, Department of Biochemistry, University of Connecticut Health Center, Farmington, CT 06030. Tel.: (860) 679-2130; Fax: (860) 679-3408.



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