RNAi Screening Implicates a SKN-1–Dependent Transcriptional Response in Stress Resistance and Longevity Deriving from Translation Inhibition 英文参考文献.docVIP

下载本文档

4
0
约 17页
2017-05-13 发布于上海
举报
版权申诉

RNAi Screening Implicates a SKN-1–Dependent Transcriptional Response in Stress Resistance and Longevity Deriving from Translation Inhibition 英文参考文献.doc

1、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

RNAi Screening Implicates a SKN-1–Dependent Transcriptional Response in Stress Resistance and Longevity Deriving from Translation Inhibition 英文参考文献

RNAiScreeningImplicatesaSKN-1–Dependent TranscriptionalResponseinStressResistanceand LongevityDerivingfromTranslationInhibition JinlingWang1.,StaceyRobida-Stubbs1.,JenniferM.A.Tullet1¤a,Jean-Franc?ois Rual2,3¤b,MarcVidal2,3 , T.KeithBlackwell1* 1JoslinDiabetesCenter,HarvardStemCellInstitute,andDepartmentofPathology,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,2Centerfor Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America, 3Department of Genetics,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica Abstract Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for oxidative stress resistance and promotes longevityunderreducedinsulin/IGF-1–like signaling(IIS),dietary restriction(DR), andnormalconditions.SKN-1inducibly activates genes involved in detoxification, protein homeostasis, andother functions in response to stress. Herewe used genome-scale RNA interference (RNAi) screening to identify mechanisms that prevent inappropriate SKN-1 target gene expression under non-stressed conditions. We identified 41 genes for which knockdown leads to activation of a SKN-1 targetgene(gcs-1)throughskn-1-dependentorothermechanisms.Thesegenescorrespondtomultiplecellularprocesses, including mRNA translation. Inhibition of translation is known to increase longevity and stress resistance and may be importantforDR–inducedlifespanextension.Onemodelpostulatesthattheseeffectsderivefromreducedenergyneeds, but various observations suggest that specific longevity pathways are involved. Here we show that translation initiation factorRNAirobustlyinducesSKN-1targetgenetranscriptionandconfersskn-1-dependentoxidativestressresistance.The accompanyingincreasesinlongevityaremediatedlargelythroughtheactivitiesofSKN-1andthetranscriptionfactorDAF- 16(FOXO),whichisrequiredforlongevitythatderivesfromreducedIIS.OurresultsindicatethattheSKN-1detoxification genenet