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For instance,<jats:italic>lin-35<\/jats:italic>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We used the ORFeome RNAi library to identify genes that interact with<jats:italic>C. elegans lin-35<\/jats:italic>Rb and identified 57 genes that showed synthetic or enhanced RNAi phenotypes in<jats:italic>lin-35<\/jats:italic>mutants as compared to<jats:italic>rrf-3<\/jats:italic>and<jats:italic>eri-1<\/jats:italic>RNAi hypersensitive mutants. Based on characterizations of a deletion allele, the synthetic<jats:italic>lin-35<\/jats:italic>interactor<jats:italic>zfp-2<\/jats:italic>was found to suppress RNAi and to cooperate with<jats:italic>lin-35<\/jats:italic>Rb in somatic gonad development. Interestingly, ten splicing-related genes were found to function similar to<jats:italic>lin-35<\/jats:italic>Rb, as synMuv B genes that prevent inappropriate vulval induction. Partial inactivation of specific spliceosome components revealed further similarities with<jats:italic>lin-35<\/jats:italic>Rb functions in cell-cycle control, transgene expression and restricted expression of germline granules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified an extensive series of candidate<jats:italic>lin-35<\/jats:italic>Rb interacting genes and validated<jats:italic>zfp-2<\/jats:italic>as a novel<jats:italic>lin-35<\/jats:italic>synthetic lethal gene. In addition, we observed a novel role for a subset of splicing components in<jats:italic>lin-35<\/jats:italic>Rb-controlled processes. Our data support novel hypotheses about possibilities for anti-cancer therapies and multilevel regulation of gene expression.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-213x-7-30","type":"journal-article","created":{"date-parts":[[2007,4,30]],"date-time":"2007-04-30T15:51:47Z","timestamp":1177948307000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["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"],"prefix":"10.1186","volume":"7","author":[{"given":"Julian","family":"Ceron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Rual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Chandra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Dupuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"van den Heuvel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,4,6]]},"reference":[{"issue":"6089","key":"172_CR1","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/323643a0","volume":"323","author":"SH Friend","year":"1986","unstructured":"Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP: A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. 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