A small upstream open reading frame causes inhibition of human major vaultprotein expression from a ubiquitous mRNA splice variant

Overexpression of the major vault protein (MVP) has been linked to a multid rug resistance (MDR) phenotype. We describe a ubiquitously expressed MVP mR NA splice variant (long (L)-MVP) differing from the regular isoform (short (S)MVP) within the 5'-leader. Only L-MVP mRNA contains a small upstream ope n reading frame which was proven to inhibit in vitro and in vivo MVP expres sion in cis, L-MVP represented an almost constant portion of total MVP mRNA in diverse normal tissues, but was more variable in malignant cell types. MDR sublines with altered MVP expression displaced changed S-MVP/L-MVP rati os as compared to their drug-sensitive counterparts. Our results suggest al ternative splicing as one mechanism for regulation of R MVP expression. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier S cience B,V, All rights reserved.