Expression of basement membrane proteins: evidence for complex post-transcriptional control mechanisms

Differentiated murine teratocarcinoma cell lines have been widely used as sources for the basement membrane proteins laminin and collagen IV. In order to understand the control of their expression, we have measured the transcription rates of the corresponding genes in nuclear run-on assays. The ratios of transcripts obtained from the five different genes of interest (for laminins A, B1, and B2 and alpha 1(IV), alpha 2(IV)) are rather different from the ratios of the corresponding mRNAs, which are again different from the protein levels needed. The gene for alpha 2(IV) is transcribed at a higher rate than the one for alpha 1(IV) and, similarly, the gene for laminin A is transcribed at a higher rate than the other two laminin genes, respectively. However, the alpha 2(IV) and laminin A mRNA levels are lower than those for the other chains of the same molecule. The alpha 1(IV) mRNA is 3- to 15-fold more abundant than the alpha 2(IV) mRNA, depending on the cell line. At the protein level, the A chain seems to be limiting for the assembly of laminin, in accordance with its low mRNA level. The two collagen chains have variable pool sizes, but the triple helical molecules always seem to be composed of two alpha 1(IV) and one alpha 2(IV) chains. These results point to extensive control mechanisms at various stages of posttranscriptional events, some of which we could identify.