《Nature》：RNA干涉过程中“小干涉RNA”的识别
RNA干涉是在演化中保留下来的一个过程，通过该过程，双链RNA诱导目标基因的沉寂，它已迅速成为阻断基因活性的标准实验技术。“小干涉RNA”（siRNA）由约20 个碱基对组成，有5个磷酸盐、2个核苷和3个悬臂，在RNA沉寂通道中扮演中心角色，是瞄准特定信使RNA进行降解的指导要素。现在，结构研究确定，PAZ （Argonaute蛋白家族特有的一个区域，该家族的蛋白与RNA沉寂机制有关）专门识别siRNA，方法是通过将siRNA的3个悬臂固定.
Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain
JIN-BIAO MA*, KEQIONG YE* & DINSHAW J. PATEL
Short RNAs mediate gene silencing, a process associated with virus resistance, developmental control and heterochromatin formation in eukaryotes. RNA silencing is initiated through Dicer-mediated processing of double-stranded RNA into small interfering RNA (siRNA). The siRNA guide strand associates with the Argonaute protein in silencing effector complexes, recognizes complementary sequences and targets them for silencing. The PAZ domain is an RNA-binding module found in Argonaute and some Dicer proteins and its structure has been determined in the free state. Here, we report the 2.6 Å crystal structure of the PAZ domain from human Argonaute eIF2c1 bound to both ends of a 9-mer siRNA-like duplex. In a sequence-independent manner, PAZ anchors the 2-nucleotide 3' overhang of the siRNA-like duplex within a highly conserved binding pocket, and secures the duplex by binding the 7-nucleotide phosphodiester backbone of the overhang-containing strand and capping the 5'-terminal residue of the complementary strand. On the basis of the structure and on binding assays, we propose that PAZ might serve as an siRNA-end-binding module for siRNA transfer in the RNA silencing pathway, and as an anchoring site for the 3' end of guide RNA within silencing effector complexes.
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