7zpj

From Proteopedia

Jump to: navigation, search

Mammalian Dicer in the "pre-dicing state" with pre-miR-15a substrate and TARBP2 subunit

Structural highlights

7zpj is a 3 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.81Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRBP2_MOUSE Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. May also play a role in the production of short interfering RNAs (siRNAs) from double-stranded RNA (dsRNA) by DICER1 (By similarity). Binds in vitro to the PRM1 3'-UTR (PubMed:8649414). Seems to act as a repressor of translation (PubMed:8649414). For some pre-miRNA substrates, may also alter the choice of cleavage site by DICER1 (PubMed:23063653). Negatively regulates IRF7-mediated IFN-beta signaling triggered by viral infection by inhibiting the phosphorylation of IRF7 and promoting its 'Lys'-48-linked ubiquitination and degradation (By similarity).[HAMAP-Rule:MF_03034][1] [2]

Publication Abstract from PubMed

MicroRNA (miRNA) and RNA interference (RNAi) pathways rely on small RNAs produced by Dicer endonucleases. Mammalian Dicer primarily supports the essential gene-regulating miRNA pathway, but how it is specifically adapted to miRNA biogenesis is unknown. We show that the adaptation entails a unique structural role of Dicer's DExD/H helicase domain. Although mice tolerate loss of its putative ATPase function, the complete absence of the domain is lethal because it assures high-fidelity miRNA biogenesis. Structures of murine Dicer*-miRNA precursor complexes revealed that the DExD/H domain has a helicase-unrelated structural function. It locks Dicer in a closed state, which facilitates miRNA precursor selection. Transition to a cleavage-competent open state is stimulated by Dicer-binding protein TARBP2. Absence of the DExD/H domain or its mutations unlocks the closed state, reduces substrate selectivity, and activates RNAi. Thus, the DExD/H domain structurally contributes to mammalian miRNA biogenesis and underlies mechanistical partitioning of miRNA and RNAi pathways.

Structural and functional basis of mammalian microRNA biogenesis by Dicer.,Zapletal D, Taborska E, Pasulka J, Malik R, Kubicek K, Zanova M, Much C, Sebesta M, Buccheri V, Horvat F, Jenickova I, Prochazkova M, Prochazka J, Pinkas M, Novacek J, Joseph DF, Sedlacek R, Bernecky C, O'Carroll D, Stefl R, Svoboda P Mol Cell. 2022 Nov 3;82(21):4064-4079.e13. doi: 10.1016/j.molcel.2022.10.010. PMID:36332606[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
8 reviews cite this structure
microRNAs in action: biogenesis, function and regulation.
Shang et al. (2023)
7 more
12 other articles
No citations found

See Also

References

  1. ↑ Fukunaga R, Han BW, Hung JH, Xu J, Weng Z, Zamore PD. Dicer partner proteins tune the length of mature miRNAs in flies and mammals. Cell. 2012 Oct 26;151(3):533-46. PMID:23063653 doi:10.1016/j.cell.2012.09.027
  2. ↑ Lee K, Fajardo MA, Braun RE. A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor. Mol Cell Biol. 1996 Jun;16(6):3023-34. PMID:8649414 doi:10.1128/MCB.16.6.3023
  3. ↑ Zapletal D, Taborska E, Pasulka J, Malik R, Kubicek K, Zanova M, Much C, Sebesta M, Buccheri V, Horvat F, Jenickova I, Prochazkova M, Prochazka J, Pinkas M, Novacek J, Joseph DF, Sedlacek R, Bernecky C, O'Carroll D, Stefl R, Svoboda P. Structural and functional basis of mammalian microRNA biogenesis by Dicer. Mol Cell. 2022 Nov 3;82(21):4064-4079.e13. doi: 10.1016/j.molcel.2022.10.010. PMID:36332606 doi:http://dx.doi.org/10.1016/j.molcel.2022.10.010

Contents


PDB ID 7zpj

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/7zpj"
Personal tools