The chick alpha2(I) collagen gene contains two functional promoters, and its expression in chondrocytes is regulated at both transcriptional and post-transcriptional levels.
Embryonic chick cartilages contain transcripts derived from the alpha2(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 alpha2(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 alpha2(I) collagen mRNA may also be due in part to decreased mRNA stability. Thus, repression of alpha2(I) collagen synthesis in cartilage involves both transcriptional and post-transcriptional mechanisms. In contrast, repression of alpha1(I) collagen synthesis appears to be mediated primarily at the level of transcription.
Pallante
K M
KM
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6003, USA.
Niu
Z
Z
Zhao
Y
Y
Cohen
A J
AJ
Nah
H D
HD
Adams
S L
SL
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics*; D003609:Dactinomycin / Q000494:pharmacology; D005347:Fibroblasts; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis; D016364:Reading Frames; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D003609:Dactinomycin; D003094:Collagen