英國愛丁堡大學生物科學院,,Wellcome Trust細胞生物學細胞生物學研究中心,,日本島根大學醫(yī)學院生物化學系,瑞典索德托恩大學院生物科學和醫(yī)學營養(yǎng)系卡洛琳斯卡學院的科學家在RNAi技術(shù)方面取得新的研究進展,,相關(guān)成果公布在10月24日Science上,。
在裂殖酵母的異染色質(zhì)形成過程中直接受RNA干擾程序調(diào)控。來自著絲粒重復(fù)序列的非編碼轉(zhuǎn)錄子形成小的干擾RNAs(siRNAs),,這些siRNAs直接參與RNA誘導(dǎo)的轉(zhuǎn)錄沉默程序,,是著絲粒轉(zhuǎn)錄的效應(yīng)器,最終導(dǎo)致組蛋白H3賴氨酸9甲基轉(zhuǎn)移酶Clr4基因沉默,。
研究小組發(fā)現(xiàn),,特殊的剪切因子缺陷對剪切因子本身沒有影響,但是會影響著絲粒siRNA的形成,,影響著絲粒異染色質(zhì)的完整性,。更嚴重的是,剪切因子與Cid12具有物理上的連接作用,,Cid12是RNAi沉默機制中必不可少的組件,,一旦出現(xiàn)異常會導(dǎo)致RNAi調(diào)控過程受阻,。
研究者得出結(jié)論,剪接復(fù)合物為siRNA的形成提供了一個平臺,,也促進了著絲粒重復(fù)沉默的效率,。(生物谷Bioon.com)
生物谷推薦原始出處:
Science 24 October 2008:DOI: 10.1126/science.1164029
Splicing Factors Facilitate RNAi-Directed Silencing in Fission Yeast
Elizabeth H. Bayne,1 Manuela Portoso,1* Alexander Kagansky,1 Isabelle C. Kos-Braun,1 Takeshi Urano,2 Karl Ekwall,3 Flavia Alves,1 Juri Rappsilber,1 Robin C. Allshire1
Heterochromatin formation at fission yeast centromeres is directed by RNA interference (RNAi). Noncoding transcripts derived from centromeric repeats are processed into small interfering RNAs (siRNAs) that direct the RNA-induced transcriptional silencing (RITS) effector complex to engage centromere transcripts, resulting in recruitment of the histone H3 lysine 9 methyltransferase Clr4, and hence silencing. We have found that defects in specific splicing factors, but not splicing itself, affect the generation of centromeric siRNAs and consequently centromeric heterochromatin integrity. Moreover, splicing factors physically associate with Cid12, a component of the RNAi machinery, and with centromeric chromatin, consistent with a direct role in RNAi. We propose that spliceosomal complexes provide a platform for siRNA generation and hence facilitate effective centromere repeat silencing.
1 Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, 6.34 Swann Building, Edinburgh EH9 3JR, UK.
2 Department of Biochemistry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan.
3 Karolinska Institute, Department of Biosciences and Medical Nutrition, University College Sodertorn, Novum 141, 57 Huddinge, Sweden.