User:Irfan Saleh/sandbox 1

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Article Name

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

Background Information

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

RNA silencing refers to a conserved sequence-specific gene regulation mechanism mediated by small RNA molecules ( 1 ). RNA silencing plays a fundamental role in many important biological processes in eukaryotes, including host gene regulation and defense against invading foreign nucleic acids

Protein Name

Name: 2EZ6

The protein 2ez6 seems to be first discovered in the "Aquifex aeolicus" is a rod-shaped bacterium with a length of 2 to 6 micrometers and a diameter of around half a micrometer.The protein itself is a 2ez6 is a 4 chain structure with a sequence form.

Protein Function

Members of the ribonuclease III (RNase III) family are double-stranded RNA (dsRNA) specific endoribonucleases characterized by a signature motif in their active centers and a two-base 3' overhang in their products. While Dicer, which produces small interfering RNAs, is currently the focus of intense interest, the structurally simpler bacterial RNase III serves as a paradigm for the entire family. Here, we present the crystal structure of an RNase III-product complex, the first catalytic complex observed for the family. A 7 residue linker within the protein facilitates induced fit in protein-RNA recognition. A pattern of protein-RNA interactions, defined by four RNA binding motifs in RNase III and three protein-interacting boxes in dsRNA, is responsible for substrate specificity, while conserved amino acid residues and divalent cations are responsible for scissile-bond cleavage. The structure reveals a wealth of information about the mechanism of RNA hydrolysis that can be extrapolated to other RNase III family members.

Relevance

2EZ6 - Crystal structure of Aquifex aeolicus RNase III (D44N) complexed with product of double-stranded RNA processing. It is an important part of RNA processig because the RNA copy of a protein encoding gene must be modified in several ways before it can be transported out of the nucleus and translated into protein. Meanwhile RNA

Structural Highlights

This link show this part of the protein

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