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

Authors
Journal
FEBS Letters
0014-5793
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
494
Identifiers
DOI: 10.1016/s0014-5793(01)02318-3
Keywords
  • Major Vault Protein
  • Lung Resistance Protein
  • Alternative Splicing
  • 5′-Untranslated Region
  • Upstream Open Reading Frame
  • Translational Repression
Disciplines
  • Biology
  • Medicine

Abstract

Abstract 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.

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