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A small upstream open reading frame causes inhibition of human major vault protein expression from a ubiquitous mRNA splice variant
Author(s) -
Holzmann Klaus,
Ambrosch Ingo,
Elbling Leonilla,
Micksche Michael,
Berger Walter
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02318-3
Subject(s) - open reading frame , messenger rna , biology , upstream open reading frame , splice , microbiology and biotechnology , rna splicing , gene isoform , alternative splicing , gene , genetics , translation (biology) , rna , peptide sequence
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.