Abstract
RNA-induced silencing complex (RISC) plays a critical role in small interfering RNA (siRNA) and microRNAs (miRNA) pathways. Accumulating evidence has demonstrated that the major RISC members (AGO, DICER, TRBP, PACT and GW182) represent expression discrepancies or multiple orthologues/paralogues in different species. To elucidate their evolutionary characteristics, an integrated evolutionary analysis was performed. Here, animal and plant AGOs were divided into three classes (multifunctional AGOs, siRNA-associated AGOs and piRNA-associated AGOs for animal AGOs and multifunctional AGOs, siRNA-associated AGOs and complementary functioning AGOs for plant AGOs). Animal and plant DICERs were grouped into one class (multifunctional DICERs) and two classes (multifunctional DICERs and siRNA-associated DICERs), respectively. Protista/fungi AGOs or DICERs were specifically associated with the siRNA pathway. Additionally, TRBP/PACT/GW182 were identified only in animals, and all of them functioned in the miRNA pathway. Mammalian AGOs, animal DICERs and chordate TRBP/PACT were found to be monophyletic. A large number of gene duplications were identified in AGO and DICER groups. Taken together, we provide a comprehensive evolutionary analysis, describe a phylogenetic tree-based classification of the major RISC members and quantify their gene duplication events. These findings are potentially useful for classifying RISCs, optimizing species-specific RISCs and developing research model organisms.
Highlights
The major members of RNA-induced silencing complex (RISC) have been identified and characterized, including AGO, DICER, TRBP (TARBP2), PACT (PRKRA) and GW182 (GAWKY)
TRBP/PACT found in RISC binds to double-stranded RNAs and ensures regular miRNA biogenesis[12,13]
GW182 directly interacts with AGO2, and GW182 proteins are essential for miRNA-guided gene silencing in various organisms
Summary
The major members of RISC have been identified and characterized, including AGO (argonaute), DICER, TRBP (TARBP2), PACT (PRKRA) and GW182 (GAWKY). A member of the RNase III family, processes miRNA precursors (pre-miRNAs) to mature miRNAs. Recent studies have demonstrated that AGO/DICER are not required for guide hairpin RNA function[10,11]. Within the RISC loading complex, DICER/TRBP assists in processing pre-miRNAs to mature miRNAs and load them onto AGO2. Several conclusions are summarized as follows: (I) vertebrates lack siRNA-class AGO proteins and vertebrate AGOs display low rates of molecular evolution[15]; (II) Dicers might have duplicated and diversified independently and have evolved for various functions in invertebrates[16]; (III) Loquacious identified in insects may be ancestral to both TRBP and PACT; www.nature.com/scientificreports/. We applied improved and integrated bioinformatic softwares/algorithms for investigating the evolution of the major RISC members, and these results provide a novel insight into RISC evolution and RISC-mediated gene regulation
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