Abstract
The repressive effect of the 3'-untranslated region (3'-UTR) in human connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) mRNA on gene expression had been demonstrated in our previous study. Here, we identified a minimal RNA element in the 3'-UTR, which acts as a cis-acting element of structure-anchored repression (CAESAR). Deletion analyses of the 3'-UTR led us to minimize the element of 84 bases at the junction of the coding region and the 3'-UTR. The minimized RNA segment is predicted, and actually capable of forming a stable secondary structure in vitro. Mutational analyses disclosed a significant relationship between the predicted structure and repressive effect. The utility of CAESAR as a post-transcriptional regulatory element was represented by the fact that steady-state mRNA levels were not affected by CAESAR linked in cis, while protein levels from such a chimeric gene were markedly reduced. Of note, the CAESAR sequence exerted no effect, when it was placed upstream of the promoter. Finally, RNA gel electromobility-shift analyses demonstrated a nuclear factor that interacts with the folded CAESAR. Taken together, it was uncovered that CAESAR of ctgf is a novel post-transcriptional structured RNA regulatory element, probably acting through direct interactions with a nuclear factor as observed in retroviral RNA elements with certain proteins.
| Original language | English |
|---|---|
| Pages (from-to) | 4773-4786 |
| Number of pages | 14 |
| Journal | Oncogene |
| Volume | 19 |
| Issue number | 41 |
| Publication status | Published - Sep 28 2000 |
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Keywords
- 3'-UTR
- Angiogenesis
- Chondrocyte
- CTGF
- HIV-1 Rev
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene : Similarities to retroviral RNA-protein interactions. / Kubota, Satoshi; Kondo, Seiji; Eguchi, Takanori; Hattori, Takako; Nakanishi, Tohru; Pomerantz, Roger J.; Takigawa, Masaharu.
In: Oncogene, Vol. 19, No. 41, 28.09.2000, p. 4773-4786.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene
T2 - Similarities to retroviral RNA-protein interactions
AU - Kubota, Satoshi
AU - Kondo, Seiji
AU - Eguchi, Takanori
AU - Hattori, Takako
AU - Nakanishi, Tohru
AU - Pomerantz, Roger J.
AU - Takigawa, Masaharu
PY - 2000/9/28
Y1 - 2000/9/28
N2 - The repressive effect of the 3'-untranslated region (3'-UTR) in human connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) mRNA on gene expression had been demonstrated in our previous study. Here, we identified a minimal RNA element in the 3'-UTR, which acts as a cis-acting element of structure-anchored repression (CAESAR). Deletion analyses of the 3'-UTR led us to minimize the element of 84 bases at the junction of the coding region and the 3'-UTR. The minimized RNA segment is predicted, and actually capable of forming a stable secondary structure in vitro. Mutational analyses disclosed a significant relationship between the predicted structure and repressive effect. The utility of CAESAR as a post-transcriptional regulatory element was represented by the fact that steady-state mRNA levels were not affected by CAESAR linked in cis, while protein levels from such a chimeric gene were markedly reduced. Of note, the CAESAR sequence exerted no effect, when it was placed upstream of the promoter. Finally, RNA gel electromobility-shift analyses demonstrated a nuclear factor that interacts with the folded CAESAR. Taken together, it was uncovered that CAESAR of ctgf is a novel post-transcriptional structured RNA regulatory element, probably acting through direct interactions with a nuclear factor as observed in retroviral RNA elements with certain proteins.
AB - The repressive effect of the 3'-untranslated region (3'-UTR) in human connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) mRNA on gene expression had been demonstrated in our previous study. Here, we identified a minimal RNA element in the 3'-UTR, which acts as a cis-acting element of structure-anchored repression (CAESAR). Deletion analyses of the 3'-UTR led us to minimize the element of 84 bases at the junction of the coding region and the 3'-UTR. The minimized RNA segment is predicted, and actually capable of forming a stable secondary structure in vitro. Mutational analyses disclosed a significant relationship between the predicted structure and repressive effect. The utility of CAESAR as a post-transcriptional regulatory element was represented by the fact that steady-state mRNA levels were not affected by CAESAR linked in cis, while protein levels from such a chimeric gene were markedly reduced. Of note, the CAESAR sequence exerted no effect, when it was placed upstream of the promoter. Finally, RNA gel electromobility-shift analyses demonstrated a nuclear factor that interacts with the folded CAESAR. Taken together, it was uncovered that CAESAR of ctgf is a novel post-transcriptional structured RNA regulatory element, probably acting through direct interactions with a nuclear factor as observed in retroviral RNA elements with certain proteins.
KW - 3'-UTR
KW - Angiogenesis
KW - Chondrocyte
KW - CTGF
KW - HIV-1 Rev
UR - http://www.scopus.com/inward/record.url?scp=0034726967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034726967&partnerID=8YFLogxK
M3 - Article
VL - 19
SP - 4773
EP - 4786
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 41
ER -