Expression of two protein isoforms of PAX7 is controlled by competing cleavage-polyadenylation and splicing.
The PAX7 gene encodes an evolutionary conserved transcription factor that is involved in the determination of the myogenic cell lineage during the development of vertebrates. In the postnatal period, the function of PAX7 is ultimately required for the specification of muscle satellite cells. The fact that PAX7 is expressed in fast proliferating embryonal myoblasts and in quiescent satellite cells of adults raised the question whether different PAX7 protein isoforms may have distinct roles in these myogenic precursors. Previously, we identified a human PAX7 mRNA encoding a C-terminus which did not show any sequence similarity to the PAX7 proteins of other organisms. So far, there was no further information available concerning the biological nature and significance of this form of PAX7. Here, we show that expression of PAX7 can be regulated by differential transcriptional termination either in exon 9 or in exon 8. Thereby, differential mRNA cleavage-polyadenylation and splicing of PAX7 may result in production of two alternative protein forms that contain or exclude the evolutionary conserved carboxy-terminal domain, respectively. The existence of both protein isoforms in vivo was confirmed by Western blot analysis. These data imply that the alternative C-termini of PAX7 may convey different functions to the corresponding protein isoforms.
Vorobyov
Eugene
E
Institut für Humangenetik, Universitätsklinikum, Münster, Germany.
Horst
Jürgen
J
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D051763:PAX7 Transcription Factor; D011061:Poly A / Q000235:genetics*; D026723:Polyadenylation / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000235:genetics
D018398:Homeodomain Proteins; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; C497322:Pax7 protein, mouse; D020033:Protein Isoforms; D011061:Poly A