論文 - 詳細
| RRC ID | 3563 |
|---|---|
| 著者 | Ceron J, Rual JF, Chandra A, Dupuy D, Vidal M, van den Heuvel S. |
| タイトル | Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity. |
| ジャーナル | BMC Dev Biol |
| Abstract |
BACKGROUND:The retinoblastoma tumor suppressor (Rb) acts in a conserved pathway that is deregulated in most human cancers. Inactivation of the single Rb-related gene in Caenorhabditis elegans, lin-35, has only limited effects on viability and fertility, yet causes changes in cell-fate and cell-cycle regulation when combined with inactivation of specific other genes. For instance, lin-35 Rb is a synthetic multivulva (synMuv) class B gene, which causes a multivulva phenotype when inactivated simultaneously with a class A or C synMuv gene. RESULTS:We used the ORFeome RNAi library to identify genes that interact with C. elegans lin-35 Rb and identified 57 genes that showed synthetic or enhanced RNAi phenotypes in lin-35 mutants as compared to rrf-3 and eri-1 RNAi hypersensitive mutants. Based on characterizations of a deletion allele, the synthetic lin-35 interactor zfp-2 was found to suppress RNAi and to cooperate with lin-35 Rb in somatic gonad development. Interestingly, ten splicing-related genes were found to function similar to lin-35 Rb, as synMuv B genes that prevent inappropriate vulval induction. Partial inactivation of specific spliceosome components revealed further similarities with lin-35 Rb functions in cell-cycle control, transgene expression and restricted expression of germline granules. CONCLUSION:We identified an extensive series of candidate lin-35 Rb interacting genes and validated zfp-2 as a novel lin-35 synthetic lethal gene. In addition, we observed a novel role for a subset of splicing components in lin-35 Rb-controlled processes. Our data support novel hypotheses about possibilities for anti-cancer therapies and multilevel regulation of gene expression. |
| 巻・号 | 7 |
| ページ | 30 |
| 公開日 | 2007-4-6 |
| DOI | 10.1186/1471-213X-7-30 |
| PII | 1471-213X-7-30 |
| PMID | 17417969 |
| PMC | PMC1863419 |
| MeSH | Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics* Female Gene Expression Regulation, Developmental Genes, Helminth* Phenotype RNA Interference* RNA, Double-Stranded / genetics RNA, Helminth / genetics Repressor Proteins / genetics* Retinoblastoma Protein / genetics* Spliceosomes / genetics Vulva / growth & development Zinc Fingers / genetics |
| IF | 2.0 |
| 引用数 | 72 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY |
| リソース情報 | |
| 線虫 | tm1111 tm557 |