Analysis of the intron-exon organization of the human multidrug-resistance protein gene (MRP) and alternative splicing of its mRNA

Genomics. 1997 Oct 15;45(2):368-78. doi: 10.1006/geno.1997.4950.


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. MRP is 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 of MRP and 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.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Chromosomes, Human, Pair 16 / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • DNA / genetics
  • DNA Primers / genetics
  • Evolution, Molecular
  • Exons
  • Genes, MDR*
  • Humans
  • Introns
  • Molecular Sequence Data
  • Multidrug Resistance-Associated Proteins
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Restriction Mapping
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid


  • ATP-Binding Cassette Transporters
  • CFTR protein, human
  • DNA Primers
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • DNA

Associated data

  • GENBANK/AF017145
  • GENBANK/AF022824
  • GENBANK/AF022825
  • GENBANK/AF022826
  • GENBANK/AF022827
  • GENBANK/AF022828
  • GENBANK/AF022829
  • GENBANK/AF022830
  • GENBANK/AF022831
  • GENBANK/AF022832
  • GENBANK/AF022833
  • GENBANK/AF022834
  • GENBANK/AF022835
  • GENBANK/AF022836
  • GENBANK/AF022837
  • GENBANK/AF022838
  • GENBANK/AF022839
  • GENBANK/AF022840
  • GENBANK/AF022841
  • GENBANK/AF022842
  • GENBANK/AF022843
  • GENBANK/AF022844
  • GENBANK/AF022845
  • GENBANK/AF022846
  • GENBANK/AF022847
  • GENBANK/AF022848
  • GENBANK/AF022849