7swf | pdb_00007swf
Cryo-EM structure of Arabidopsis Ago10-guide-target RNA complex in a central duplex conformation
Structural highlights
Function[AGO10_ARATH] Involved in RNA-mediated post-transcriptional gene silencing (PTGS). Main component of the RNA-induced silencing complex (RISC) that binds to a short guide RNA such as a microRNA (miRNA) or small interfering RNA (siRNA). RISC uses the mature miRNA or siRNA as a guide for slicer-directed cleavage of homologous mRNAs to repress gene expression. Required for reliable formation of primary and axillary shoot apical meristems. Specifies leaf adaxial identity by repressing the miR165 and miR166 microRNAs in the embryonic shoot apex, in the shoot apical meristem (SAM) and leaf. Represses the microRNA miR398 which targets CCS1 chaperone mRNAs for translational inhibition. Acts as a negative regulator of AGO1 protein level. Like AGO1, is required for stem cell function and organ polarity. Unlike AGO1, is not subjected to small RNA-mediated repression itself. Essential for multiple processes in development. Coregulates, with GATA18/HAN, the shoot apical meristem (SAM) organization (PubMed:26390296).[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedSmall RNAs (sRNAs), including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are essential gene regulators for plant and animal development. The loading of sRNA duplexes into the proper ARGONAUTE (AGO) protein is a key step to forming a functional silencing complex. In Arabidopsis thaliana, the specific loading of miR166/165 into AGO10 (AtAGO10) is critical for the maintenance of the shoot apical meristem, the source of all shoot organs, but the mechanism by which AtAGO10 distinguishes miR166/165 from other cellular miRNAs is not known. Here, we show purified AtAGO10 alone lacks loading selectivity towards miR166/165 duplexes. However, phosphate and HSP chaperone systems reshape the selectivity of AtAGO10 to its physiological substrates. A loop in the AtAGO10 central cleft is essential for recognizing specific mismatches opposite the guide strand 3' region in miR166/165 duplexes. Replacing this loop with the equivalent loop from Homo sapiens AGO2 (HsAGO2) changes AtAGO10 miRNA loading behavior such that 3' region mismatches are ignored and mismatches opposite the guide 5' end instead drive loading, as in HsAGO2. Thus, this study uncovers the molecular mechanism underlying the miR166/165 selectivity of AtAGO10, essential for plant development, and provides new insights into how miRNA duplex structures are recognized for sRNA sorting. The molecular mechanism of microRNA duplex selectivity of Arabidopsis ARGONAUTE10.,Xiao Y, MacRae IJ Nucleic Acids Res. 2022 Jul 8. pii: 6633885. doi: 10.1093/nar/gkac571. PMID:35801914[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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