A small upstream open reading frame causes inhibition of human major vault protein expression from a ubiquitous mRNA splice variant.
Overexpression of the major vault protein (MVP) has been linked to a multidrug resistance (MDR) phenotype. We describe a ubiquitously expressed MVP mRNA 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 open reading frame which was proven to inhibit in vitro and in vivo MVP expression 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 displayed changed S-MVP/L-MVP ratios as compared to their drug-sensitive counterparts. Our results suggest alternative splicing as one mechanism for regulation of MVP expression.
Holzmann
K
K
Division of Cell Biology, Institute of Cancer Research, Vienna University, Austria.
Ambrosch
I
I
Elbling
L
L
Micksche
M
M
Berger
W
W
D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary; D018432:Drug Resistance, Multiple / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D012333:RNA, Messenger; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D000099187:Major Vault Protein
D020121:5' Untranslated Regions; D018076:DNA, Complementary; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein