來自哈佛大學醫(yī)學院細胞生物學系，哈佛大學醫(yī)學院Howard Hughes醫(yī)學研究所的科學家Danesh Moazed與Mario Halic在最新一期的Cell雜志上發(fā)表研究新進展文章,，解析一種原始的RNA形成影響RNAi激活與異染色體形成的機制,。
Danesh Moazed研究組以裂殖酵母為研究模型，他們發(fā)現(xiàn)重復性的異染色質(zhì)的蓄積形成與干擾性RNA（siRNA）的形成這兩個過程可相互影響,。但是,，這兩個獨立的生物學過程是如何相互影響，并且整個過程中的正負反饋回路是如何組成的,，這些問題都困擾著科學家,。
顯然,，這是個基礎研究問題，在本Cell文章中,，Danesh Moazed研究小組試圖解開這個謎題,，他們發(fā)現(xiàn)兩個獨立的Argonaute（Ago1）介導的通路影響小RNA的產(chǎn)生。RNA依耐性RNA聚合酶復合物（RNA-dependent RNA polymerase complex,，RDRC）和Dicer在特殊的非編碼RNA的產(chǎn)生過程中發(fā)揮著重要的作用,，它們通過Ago1獨立于異染色質(zhì)的途徑影響siRNA的形成。
在RDRC或是Dicer缺乏的情況下,，一類獨特的小RNA,，名為原始小RNA（primal small RNA，priRNAs）與Ago1結(jié)合,，其后priRNAs降解生成大量的轉(zhuǎn)錄產(chǎn)物,，這些產(chǎn)物可以與Ago1結(jié)合，并以反義轉(zhuǎn)錄產(chǎn)物為靶位,。
這些研究結(jié)果表明,，細胞中的轉(zhuǎn)錄監(jiān)控與RNA降解產(chǎn)物-Ago1誘導的激發(fā)siRNA產(chǎn)生功能有關。 （生物谷Bioon.com）
生物谷推薦原始出處：
Cell, Volume 140, Issue 4, 504-516, 19 February 2010 DOI:10.1016/j.cell.2010.01.019
Dicer-Independent Primal RNAs Trigger RNAi and Heterochromatin Formation
Mario Halic, Danesh Moazed
Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, 02115, USA Corresponding author
Assembly of fission yeast pericentromeric heterochromatin and generation of small interfering RNAs (siRNAs) from noncoding centromeric transcripts are mutually dependent processes. How this interdependent positive feedback loop is first triggered is a fundamental unanswered question. Here, we show that two distinct Argonaute (Ago1)-dependent pathways mediate small RNA generation. RNA-dependent RNA polymerase complex (RDRC) and Dicer act on specific noncoding RNAs to generate siRNAs by a mechanism that requires the slicer activity of Ago1 but is independent of pre-existing heterochromatin. In the absence of RDRC or Dicer, a distinct class of small RNAs, called primal small RNAs (priRNAs), associates with Ago1. priRNAs are degradation products of abundant transcripts, which bind to Ago1 and target antisense transcripts that result from bidirectional transcription of DNA repeats. Our results suggest that a transcriptome surveillance mechanism based on random association of RNA degradation products with Argonaute triggers siRNA amplification and heterochromatin assembly within DNA repeats.
