专题：Cell专题
来自哈佛大学医学院细胞生物学系，哈佛大学医学院Howard Hughes医学研究所的科学家Danesh Moazed与Mario Halic在最新一期的Cell杂志上发表研究新进展文章，解析一种原始的RNA形成影响RNAi激活与异染色体形成的机制。
Danesh Moazed研究组以裂殖酵母为研究模型，他们发现重复性的异染色质的蓄积形成与干扰性RNA（siRNA）的形成这两个过程可相互影响。但是，这两个独立的生物学过程是如何相互影响，并且整个过程中的正负反馈回路是如何组成的，这些问题都困扰着科学家。
显然，这是个基础研究问题，在本Cell文章中，Danesh Moazed研究小组试图解开这个谜题，他们发现两个独立的Argonaute（Ago1）介导的通路影响小RNA的产生。RNA依耐性RNA聚合酶复合物（RNA-dependent RNA polymerase complex，RDRC）和Dicer在特殊的非编码RNA的产生过程中发挥着重要的作用，它们通过Ago1独立于异染色质的途径影响siRNA的形成。
在RDRC或是Dicer缺乏的情况下，一类独特的小RNA，名为原始小RNA（primal small RNA，priRNAs）与Ago1结合，其后priRNAs降解生成大量的转录产物，这些产物可以与Ago1结合，并以反义转录产物为靶位。
这些研究结果表明，细胞中的转录监控与RNA降解产物-Ago1诱导的激发siRNA产生功能有关。 （生物谷Bioon.com）
生物谷推荐原始出处：
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.
