Volume 271, Number 41,
Issue of October 11, 1996
pp. 25233-25239
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
The Chick
2(I) Collagen Gene Contains Two Functional
Promoters, and Its Expression in Chondrocytes Is Regulated at Both
Transcriptional and Post-transcriptional Levels
(Received for publication, April 25, 1996, and in revised form, July 3, 1996)
Kim M.
Pallante
,
Zeling
Niu
,
Yufeng
Zhao
,
Arthur J.
Cohen
,
Hyun-Duck
Nah
and
Sherrill L.
Adams
From the Department of Biochemistry, School of Dental Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania 19104-6003
Embryonic chick cartilages contain transcripts
derived from the
2(I) collagen gene, although type I collagen is not
normally found in these tissues; most of these RNAs are alternative
transcripts initiating within intron 2. Use of the internal start site
results in replacement of exons 1 and 2 with a previously undescribed
exon and a change in the translational reading frame; thus, the
alternative transcript cannot encode
2(I) collagen. We have
demonstrated that production of the alternative transcript is due to
activation of an internal promoter in chondrocytes and have identified
a 179-base pair domain that is required for its activity. Furthermore,
we have shown that the alternative transcript resulting from activation
of the internal promoter turns over relatively rapidly; thus, the
steady-state level of this transcript is less than predicted based on
the transcription rate. The upstream promoter is only partially
repressed in chondrocytes, suggesting that the lack of authentic
2(I) collagen mRNA may also be due in part to decreased mRNA
stability. Thus, repression of
2(I) collagen synthesis in cartilage
involves both transcriptional and post-transcriptional mechanisms. In
contrast, repression of
1(I) collagen synthesis appears to be
mediated primarily at the level of transcription.