Expression of human collagen type IV genes is regulated by transcriptional and post-transcriptional mechanisms

The molecules of the basement membrane specific collagen type IV are heterotrimers consisting of two alpha 1(IV) and one alpha 2(IV) polypeptide chains. Comparison of the ratios of transcription by nuclear run-on analysis and mRNAs by RNAse protection assay indicates the involvement of transcriptional as well as post-transcriptional events in the control of overall collagen type IV expression. The relative ratios of transcription of the respective genes COL4A1 and COL4A2 remained near 2:1 in most cells, whereas the ratio of mRNA steady-state levels alpha 1(IV)/alpha 2(IV) varied from 0.3:1 to 1:1 and did not parallel the subunit structure of the protein. Nevertheless, secreted protein shows a 2:1 ratio of the subunit polypeptides. This indicates that post-translational processes during chain selection, aggregation and secretion finally determine the amount of secreted protein.