THE CHICK ALPHA-2(I) COLLAGEN GENE CONTAINS 2 FUNCTIONAL PROMOTERS, AND ITS EXPRESSION IN CHONDROCYTES IS REGULATED AT BOTH TRANSCRIPTIONALAND POSTTRANSCRIPTIONAL LEVELS

Embryonic chick cartilages contain transcripts derived from the alpha 2(I) collagen gene, although type I collagen is not normally found in these tissues; most of these RNAs are alternative transcripts initiati ng within intron 2, Use of the internal start site results in replacem ent of exons 1 and 2 with a previously undescribed exon and a change i n the translational reading frame; thus, the alternative transcript ca nnot encode alpha 2(I) collagen. We have demonstrated that production of the alternative transcript is due to activation of an internal prom oter in chondrocytes and have identified a 179-base pair domain that i s required for its activity, Furthermore, we have shown that the alter native transcript resulting from activation of the internal promoter t urns over relatively rapidly; thus, the steady-state level of this tra nscript is less than predicted based on the transcription rate, The up stream promoter is only partially repressed in chondrocytes, suggestin g that the lack of authentic alpha 2(I) collagen mRNA may also be due in part to decreased mRNA stability, Thus, repression of alpha 2(I) co llagen synthesis in cartilage involves both transcriptional and post-t ranscriptional mechanisms. In contrast, repression of alpha 1(I) colla gen synthesis appears to be mediated primarily at the level of transcr iption.