Elsevier

Genomics

Volume 45, Issue 2, 15 October 1997, Pages 368-378
Genomics

Regular Article
Analysis of the Intron–Exon Organization of the Human Multidrug-Resistance Protein Gene (MRP) and Alternative Splicing of Its mRNA,☆☆

https://doi.org/10.1006/geno.1997.4950Get rights and content

Abstract

Overexpression of multidrug-resistance protein (MRP) and P-glycoprotein confers similar but not identical multidrug-resistance phenotypes. However, unlike P-glycoprotein, which comprises two membrane-spanning domains (MSDs) and two nucleotide-binding domains, MRP contains a third NH2-proximal MSD, a feature now identified in several other ATP-binding cassette transmembrane transporters.MRPis located on chromosome 16 at band 13.1 close to the short-arm breakpoint of the pericentric inversion associated with the M4Eo subclass of acute myeloid leukemia. We have defined the intron–exon structure ofMRPand characterized a number of splicing variants of MRP mRNA. The gene spans at least 200 kb. It contains 31 exons and a high proportion of class 0 introns, alternative splicing of which results in significant levels of variant transcripts that maintain the original open reading frame of MRP mRNA. Analyses of the conservation of intron–exon organization and protein primary structure suggest that the MRP-related transporters evolved from a common ancestor shared with the cystic fibrosis transmembrane conductance regulator, by fusion with one or more genes encoding polytopic membrane proteins.

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    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under the following Accession Nos.: human MRP, L05628, AF017145, AF022824–AF022853; murine mrp, AF022908; human MOAT, U49248; rat MOAT, L49379; rabbit EBCR, Z49144; human SUR, U63421; YCF-1, L35237; Yor1/Ysr1, 1245963;LeishmaniaPgpA, X17154; human CFTR, M28668; humanSUR,L78208; humanCFTR,M55106.

    ☆☆

    J. D. Hayes, Ed.

    1

    Supported by a Medical Research Council of Canada Studentship.

    2

    To whom correspondence should be addressed at Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada K7L 3N6. Telephone: (613) 545-2981. Fax: (613) 545-6830.

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