Spatio-temporal expression of the trans-acting splicing factors SF2/ASF and heterogeneous ribonuclear proteins A1/A1(B) in the myometrium of the pregnant human uterus: A molecular mechanism for regulating regional protein isoform expression in vivo

Many of the human myometrial proteins associated with uterine quiescence an d the switch to coordinated contractions at the onset of labor exist as alt ernatively spliced isoforms. There is now extensive evidence to indicate th at the nuclear concentrations of the transacting splicing regulators SF2/AS F and hnRNP A1/A1(B) are fundamental in regulating the expression of specif ic protein isoforms derived from alternative splicing of single precursor m essenger ribonucleic acid transcripts. The question thus arose as to whethe r these factors were also involved in regulating the expression of specific myometrial protein species within different uterine regions during human g estation and parturition. SF2/ASF and hnRNP A1/A1(B) expression was therefo re determined in paired upper (corpus) and lower segment myometrial samples taken from individual women at term/during spontaneous labor and compared with nonpregnant control samples using specific monoclonal antibodies. We r eport that SF2/ASF levels were substantially increased in the lower uterine region, and this was associated with a parallel decrease in levels of hnRN P A1/A1(B) during gestation. Conversely, the opposite pattern was observed within the upper uterine region during pregnancy, where hnRNP A1/A1(B) was significantly up-regulated and SF2/ASF levels were much less than those fou nd in the lower uterine segment. The differential expression of hnRNP A1/A1 (B) and SF2/ASF in the upper and lower uterine segments may have a primary role in defining the formation of specific myometrial protein species assoc iated with the known contractile and relaxatory properties of these regions before and during parturition.