简介:Heterogeneousnuclearribonucleoproteins(hnRNPs)arespliceosomalmacromolecularassemblagesandthusactivelyparticipateinpre-mRNAmetabolism.Theyarecomposedofevolutionarilyconservedandtandemlyrepeatedmotifs,wherebothRNA-bindingandprotein-proteinrecognitionoccurtoachievecellularactivities.Byyetunknownmechanisms,theseribonucleoprotein(RNP)particlesaretargetedbyautoantibodiesandhenceplaysignificantroleinavarietyofhumansystemicautoimmunediseases.Thisfeaturemakesthemimportantprognosticmarkersintermsofmolecularepidemiologyandpathogenesisofautoimmunity.SinceRNPdomainisoneofthemostconservedandwidespreadscaffolds,evolutionalysesoftheseRNA-bindingdomainscanprovidefurthercluesondisease-specificepitopeformation.ThestudypresentedhereinrepresentsasequencecomparisonofRNA-recognitionregionsofrecentlyclonedandcharacterizedhumanhnRNPA3withthoseofotherrelevanthnRNPA/B-typeproteins.Theirimplicationsinhumanautoimmunityareparticularlyemphasized.
简介:Humantumornecrosisfactorα(hTNFα),apleiotropiccytokinewithactivitiesrangingfromhostdefensemechanismsininfectionandinjurytoseveretoxicityinsepticshockorotherrelateddiseases,isapromisingtargetfordrugscreening.UsingtheSELEX(systematicevolutionofligandsbyexponentialenrichment)process,weisolatedoligonucleotideligands(aptamers)withhighaffinitiesforhTNFα.Aptamerswereselectedfromastartingpoolof40randomizedsequencescomposedofabout1015RNAmolecules.RepresentativeaptamersweretruncatedtotheminimallengthwithhighaffinityforhTNFαandwerefurthermodifiedbyreplacementof2'-OHwith2'-Fand2'-NH2atallribopurinepositions.ThesemodifiedRNAaptamerswereresistanttonuclease.ThespecificityoftheseaptamersforhTNFαwasconfirmed,andtheiractivitytoinhibitthecytotoxicityofhTNFαonmouseL929cellswasdetermined.Resultsdemonstratedthatfour2'-NH2-modifiedaptamersboundtohTNFαwithhighaffinityandblockedthebindingofhTNFαtoitsreceptor,thusprotectingtheL929cellsfromthecytotoxicityofhTNFα.OligonucleotideaptamersdescribedherearepotentialtherapeuticsanddiagnosticsforhTNFc-relateddiseases.
简介:小RNA(sRNAs)是直接在房间施加他们的功能的非编码的抄本。sRNAs的鉴定由于清楚的顺序和结构的偏爱的缺乏是一项困难的任务。大多数sRNAs在类以内被识别在相关染色体的特定的intergenic区域。然而,几个这些区域仍然保持由于顺序相同或有势力的缺乏未注解统计鉴定工具。一台计算引擎被造了在intergenic区域以内寻找在Enterobacteriaceae染色体识别并且粗略地注解新通常认为的sRNA区域。在相关询问染色体识别类似的sRNA区域作为模板利用试验性地已知的sRNA数据和他们的flankinggenes/KEGGOrthology(击倒)数字。搜索引擎不仅有能力为特定的sRNAs定位通常认为的intergenic区域,而且有力量定位保存,洗牌或删除了在询问染色体的基因簇。因为它使用KO术语定位象sRNAs那样的机能上地重要的区域,更进一步,到另外的基因的击倒数字赋值将增加敏感。PsRNA服务者通过从兴趣的sRNA检索的信息被用于通常认为的sRNA区域的鉴定。计算引擎在http://bioserver1.physics.iisc.ernet.in/psrna/和http://bicmku.in:8081/psrna/在网上是可得到的。