8vaj | pdb_00008vaj

Human Argonaute3 bound to cityRNA and target RNA

spinqualitylabelsall models 8vaj, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8vaj is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.45Å Ligands: OMU, SRA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AGO3_HUMAN Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Proposed to be involved in stabilization of small RNA derivates (riRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent riRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4.[HAMAP-Rule:MF_03032] Publication Abstract from PubMed TinyRNAs (tyRNAs) are </=17-nt guide RNAs associated with Argonaute proteins (AGOs), and certain 14-nt cleavage-inducing tyRNAs (cityRNAs) catalytically activate human Argonaute3 (AGO3). We present the crystal structure of AGO3 in complex with a cityRNA, 14-nt miR-20a, and its complementary target, revealing a different trajectory for the guide-target duplex from that of its approximately 22-nt microRNA-associated AGO counterpart. cityRNA-loaded Argonaute2 (AGO2) and AGO3 enhance their endonuclease activity when the immediate 5' upstream region of the tyRNA target site (UTy) includes sequences with low affinity for AGO. We propose a model where cityRNA-loaded AGO2 and AGO3 efficiently cleave fully complementary tyRNA target sites unless they directly recognize the UTy. To investigate their gene silencing, we devised systems for loading endogenous AGOs with specific tyRNAs and demonstrated that, unlike microRNAs, cityRNA-mediated silencing heavily relies on target cleavage. Our study uncovered that AGO exploits cityRNAs for target recognition differently from microRNAs and alters gene silencing. Target cleavage and gene silencing by Argonautes with cityRNAs.,Zhang H, Sim G, Kehling AC, Adhav VA, Savidge A, Pastore B, Tang W, Nakanishi K Cell Rep. 2024 Oct 4;43(10):114806. doi: 10.1016/j.celrep.2024.114806. PMID:39368090 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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