Identification and Characterization of Alternative Promoters, Transcripts and Protein Isoforms of Zebrafish R2 Gene
文献类型：期刊论文
| 作者 | Shang, Hanqiao1,2; Li, Qing1; Feng, Guohui1,2; Cui, Zongbin1 |
| 刊名 | PLOS ONE
 |
| 出版日期 | 2011-08-24 |
| 卷号 | 6期号:8页码:e24089 |
| 关键词 | RIBONUCLEOTIDE REDUCTASE R2 CELL-CYCLE REGULATION DNA-DAMAGING AGENTS SMALL-SUBUNIT MESSENGER-RNA S-PHASE SACCHAROMYCES-CEREVISIAE MAMMALIAN-CELLS FISSION YEAST EXPRESSION |
| ISSN号 | 1932-6203 |
| 通讯作者 | Shang, HQ (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Hubei, Peoples R China ; zbcui@ihb.ac.cn |
| 中文摘要 | Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the de novo synthesis of deoxyribonucleoside triphosphates. Expression of RNR subunits is closely associated with DNA replication and repair. Mammalian RNR M2 subunit (R2) functions exclusively in DNA replication of normal cells due to its S phase-specific expression and late mitotic degradation. Herein, we demonstrate the control of R2 expression through alternative promoters, splicing and polyadenylation sites in zebrafish. Three functional R2 promoters were identified to generate six transcript variants with distinct 5' termini. The proximal promoter contains a conserved E2F binding site and two CCAAT boxes, which are crucial for the transcription of R2 gene during cell cycle. Activity of the distal promoter can be induced by DNA damage to generate four transcript variants through alternative splicing. In addition, two novel splice variants were found to encode distinct N-truncated R2 isoforms containing residues for enzymatic activity but no KEN box essential for its proteolysis. These two N-truncated R2 isoforms remained in the cytoplasm and were able to interact with RNR M1 subunit (R1). Thus, our results suggest that multilayered mechanisms control the differential expression and function of zebrafish R2 gene during cell cycle and under genotoxic stress. |
| 英文摘要 | Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the de novo synthesis of deoxyribonucleoside triphosphates. Expression of RNR subunits is closely associated with DNA replication and repair. Mammalian RNR M2 subunit (R2) functions exclusively in DNA replication of normal cells due to its S phase-specific expression and late mitotic degradation. Herein, we demonstrate the control of R2 expression through alternative promoters, splicing and polyadenylation sites in zebrafish. Three functional R2 promoters were identified to generate six transcript variants with distinct 5' termini. The proximal promoter contains a conserved E2F binding site and two CCAAT boxes, which are crucial for the transcription of R2 gene during cell cycle. Activity of the distal promoter can be induced by DNA damage to generate four transcript variants through alternative splicing. In addition, two novel splice variants were found to encode distinct N-truncated R2 isoforms containing residues for enzymatic activity but no KEN box essential for its proteolysis. These two N-truncated R2 isoforms remained in the cytoplasm and were able to interact with RNR M1 subunit (R1). Thus, our results suggest that multilayered mechanisms control the differential expression and function of zebrafish R2 gene during cell cycle and under genotoxic stress. |
| WOS标题词 | Science & Technology |
| 学科主题 | Life Sciences & Biomedicine - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | RIBONUCLEOTIDE REDUCTASE R2 ; CELL-CYCLE REGULATION ; DNA-DAMAGING AGENTS ; SMALL-SUBUNIT ; MESSENGER-RNA ; S-PHASE ; SACCHAROMYCES-CEREVISIAE ; MAMMALIAN-CELLS ; FISSION YEAST ; EXPRESSION |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China[30671602, 30871442]; National Basic Research Program of China[2012CB944500]; National High-tech RD (863) Program[2007AA10Z164] |
| 语种 | 英语 |
| WOS记录号 | WOS:000295832000093 |
| 公开日期 | 2011-12-22 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/16467]  |
| 专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
| 作者单位 | 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Hubei, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shang, Hanqiao,Li, Qing,Feng, Guohui,et al. Identification and Characterization of Alternative Promoters, Transcripts and Protein Isoforms of Zebrafish R2 Gene[J]. PLOS ONE,2011,6(8):e24089. |
| APA | Shang, Hanqiao,Li, Qing,Feng, Guohui,&Cui, Zongbin.(2011).Identification and Characterization of Alternative Promoters, Transcripts and Protein Isoforms of Zebrafish R2 Gene.PLOS ONE,6(8),e24089. |
| MLA | Shang, Hanqiao,et al."Identification and Characterization of Alternative Promoters, Transcripts and Protein Isoforms of Zebrafish R2 Gene".PLOS ONE 6.8(2011):e24089. |
入库方式： OAI收割
来源：水生生物研究所
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