Tomari Yukihide, Du Tingting, Zamore Phillip D
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell. 2007 Jul 27;130(2):299-308. doi: 10.1016/j.cell.2007.05.057.
In Drosophila, small interfering RNAs (siRNAs), which direct RNA interference through the Argonaute protein Ago2, are produced by a biogenesis pathway distinct from microRNAs (miRNAs), which regulate endogenous mRNA expression as guides for Ago1. Here, we report that siRNAs and miRNAs are sorted into Ago1 and Ago2 by pathways independent from the processes that produce these two classes of small RNAs. Such small-RNA sorting reflects the structure of the double-stranded assembly intermediates--the miRNA/miRNA( *) and siRNA duplexes--from which Argonaute proteins are loaded. We find that the Dcr-2/R2D2 heterodimer acts as a gatekeeper for the assembly of Ago2 complexes, promoting the incorporation of siRNAs and disfavoring miRNAs as loading substrates for Drosophila Ago2. A separate mechanism acts in parallel to favor miRNA/miRNA( *) duplexes and exclude siRNAs from assembly into Ago1 complexes. Thus, in flies small-RNA duplexes are actively sorted into Argonaute-containing complexes according to their intrinsic structures.
在果蝇中，通过AGO2蛋白介导RNA干扰的小干扰RNA（siRNA），其产生途径不同于作为AGO1的向导调节内源性mRNA表达的微小RNA（miRNA）。在此，我们报道siRNA和miRNA通过独立于产生这两类小RNA的过程的途径被分选到AGO1和AGO2中。这种小RNA分选反映了双链组装中间体的结构——miRNA/miRNA（）和siRNA双链体——AGO蛋白由此装载。我们发现Dcr-2/R2D2异二聚体作为AGO2复合物组装的守门人，促进siRNA的掺入，不利于miRNA作为果蝇AGO2的装载底物。一种独立的机制并行起作用，有利于miRNA/miRNA（）双链体，并排除siRNA组装到AGO1复合物中。因此，在果蝇中，小RNA双链体根据其内在结构被主动分选到含AGO的复合物中。
