Abstract
The 3′-untranslated region (UTR) is known to be a critical regulator of post-transcriptional events that determine the gene expression at the RNA level. The gene CCN1 is one of the classical members of the matricellular CCN family and is involved in a number of biological processes during mammalian development. In the present study, the 600-bp 3′-UTR of CCN1 was functionally characterized. Reporter gene analysis revealed that the entire 3′-UTR profoundly repressed gene expression in cis in different types of the cells, to which both the proximal and distal-halves of the 3′-UTR segments contributed almost equally. Deletion analysis of the 3′-UTR indicated a distinct functional element in the proximal half, whereas a putative target for microRNA-181s was predicted in silico in the distal half. Of note, the repressive RNA element in the proximal half was shown to be capable of forming a stable secondary structure. However, unexpectedly, a reporter construct with a tandem repeat of the predicted miR-181 targets failed to respond to miR-181a. In addition, the other major structured element predicted in the distal half was similarly characterized. To our surprise, the second element rather enhanced the reporter gene expression in cis. These results indicate the involvement of multiple regulatory elements in the CCN1 3′-UTR and suggest the complexity of the miRNA action as well as the 3′-UTR-mediated gene regulation.
| Original language | English |
|---|---|
| Pages (from-to) | 207-217 |
| Number of pages | 11 |
| Journal | Journal of Cell Communication and Signaling |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Aug 2013 |
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Keywords
- 3′-UTR
- CCN family
- CCN1
- Cyr61
- miRNA
- Post-transcriptional regulation
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Regulation of CCN1 via the 3′-untranslated region. / Nakagawa, Yosuke; Minato, Masanao; Sumiyoshi, Kumi; Maeda, Azusa; Hara, Chikako; Murase, Yurika; Nishida, Takashi; Kubota, Satoshi; Takigawa, Masaharu.
In: Journal of Cell Communication and Signaling, Vol. 7, No. 3, 08.2013, p. 207-217.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of CCN1 via the 3′-untranslated region
AU - Nakagawa, Yosuke
AU - Minato, Masanao
AU - Sumiyoshi, Kumi
AU - Maeda, Azusa
AU - Hara, Chikako
AU - Murase, Yurika
AU - Nishida, Takashi
AU - Kubota, Satoshi
AU - Takigawa, Masaharu
PY - 2013/8
Y1 - 2013/8
N2 - The 3′-untranslated region (UTR) is known to be a critical regulator of post-transcriptional events that determine the gene expression at the RNA level. The gene CCN1 is one of the classical members of the matricellular CCN family and is involved in a number of biological processes during mammalian development. In the present study, the 600-bp 3′-UTR of CCN1 was functionally characterized. Reporter gene analysis revealed that the entire 3′-UTR profoundly repressed gene expression in cis in different types of the cells, to which both the proximal and distal-halves of the 3′-UTR segments contributed almost equally. Deletion analysis of the 3′-UTR indicated a distinct functional element in the proximal half, whereas a putative target for microRNA-181s was predicted in silico in the distal half. Of note, the repressive RNA element in the proximal half was shown to be capable of forming a stable secondary structure. However, unexpectedly, a reporter construct with a tandem repeat of the predicted miR-181 targets failed to respond to miR-181a. In addition, the other major structured element predicted in the distal half was similarly characterized. To our surprise, the second element rather enhanced the reporter gene expression in cis. These results indicate the involvement of multiple regulatory elements in the CCN1 3′-UTR and suggest the complexity of the miRNA action as well as the 3′-UTR-mediated gene regulation.
AB - The 3′-untranslated region (UTR) is known to be a critical regulator of post-transcriptional events that determine the gene expression at the RNA level. The gene CCN1 is one of the classical members of the matricellular CCN family and is involved in a number of biological processes during mammalian development. In the present study, the 600-bp 3′-UTR of CCN1 was functionally characterized. Reporter gene analysis revealed that the entire 3′-UTR profoundly repressed gene expression in cis in different types of the cells, to which both the proximal and distal-halves of the 3′-UTR segments contributed almost equally. Deletion analysis of the 3′-UTR indicated a distinct functional element in the proximal half, whereas a putative target for microRNA-181s was predicted in silico in the distal half. Of note, the repressive RNA element in the proximal half was shown to be capable of forming a stable secondary structure. However, unexpectedly, a reporter construct with a tandem repeat of the predicted miR-181 targets failed to respond to miR-181a. In addition, the other major structured element predicted in the distal half was similarly characterized. To our surprise, the second element rather enhanced the reporter gene expression in cis. These results indicate the involvement of multiple regulatory elements in the CCN1 3′-UTR and suggest the complexity of the miRNA action as well as the 3′-UTR-mediated gene regulation.
KW - 3′-UTR
KW - CCN family
KW - CCN1
KW - Cyr61
KW - miRNA
KW - Post-transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=84880328286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880328286&partnerID=8YFLogxK
U2 - 10.1007/s12079-013-0202-x
DO - 10.1007/s12079-013-0202-x
M3 - Article
VL - 7
SP - 207
EP - 217
JO - Journal of Cell Communication and Signaling
JF - Journal of Cell Communication and Signaling
SN - 1873-9601
IS - 3
ER -