The interacting RNA polymerase II subunits, hRPB11 and hRPB3, are coordinately expressed in adult human tissues and down-regulated by doxorubicin.
We previously isolated the human RPB11 cDNA, encoding the 13.3 kDa subunit of RNA polymerase II, and demonstrated that expression of this subunit is modulated by doxorubicin. Using hRPB11 as bait in a yeast two-hybrid system, two cDNA variants encoding a second RNA polymerase II subunit, hRPB3, have now been isolated and characterized. These two hRPB3 mRNA species differed in 3' UTR region length, the longer transcript containing the AU-rich sequence motif that mediates mRNA degradation. Both hRPB11 and hRPB3 transcripts share a similar pattern of distribution in human adult tissues, with particularly high levels in both heart and skeletal muscle, and the expression of both is down-regulated by doxorubicin as found previously for the hRPB11 subunit. Taken together, these findings suggest that the interaction between hRPB3 and hRPB11 is fundamental for their function and that this heterodimer is involved in doxorubicin toxicity.
Fanciulli
M
M
Cell Metabolism and Pharmacokinetics Laboratory, Regina Elena Cancer Institute, Rome, Italy. fanciulli@crs.ifo.it
Bruno
T
T
Di Padova
M
M
De Angelis
R
R
Lovari
S
S
Floridi
A
A
Passananti
C
C
D000328:Adult; D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D002277:Carcinoma; D003001:Cloning, Molecular; D003110:Colonic Neoplasms; D018076:DNA, Complementary / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal; D009928:Organ Specificity; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D018076:DNA, Complementary; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D004317:Doxorubicin; C491783:POLR2C protein, human; D012319:RNA Polymerase II; C112110:RPB3 protein, S cerevisiae