PXD013054-1

PXD013054 is an original dataset announced via ProteomeXchange.

Title	miR-122-dependent binding of TNRC6 to HCV RNA
Description	The liver-specific microRNA, miR-122, is an essential host factor for replication of hepatitis C virus (HCV), an important infectious cause of chronic liver disease and hepatocellular carcinoma. miR-122 stabilizes the positive-strand HCV RNA genome and promotes viral RNA synthesis by binding two closely spaced sites (S1 and S2) near the 5’ end of the genome in association with Ago2. Ago2 is essential for both host factor activities, but whether other host proteins are involved is unknown. Using a quantitative proteomics approach, we identified TNRC6A (GW182) and its paralogs (TNRC6B and TNRC6C), as functionally important components of the miR-122/Ago2 host factor complex binding HCV RNA. Depletion of any two TNRC6 proteins reduced HCV replication in Huh-7.5 cells,but did not reduce viral RNA stability or translational activity, but rather dampened miR-122 stimulation of viral RNA synthesis. However, TNRC6 depletion had no effect on replication of HCV in which S2 was mutated so that miR-122 binds only S1, whereas it significantly enhanced replication when S1 was mutated and only S2 bound by miR-122. Consistent with this, we found that TNRC6 proteins preferentially associate with the S1 site, and that the association of Ago2 with S2 is increased in TNRC6-depleted cells. Collectively, these data suggest a model in which TNRC6 proteins, which are known to interact with Ago2, preferentially direct the miR-122/Ago2 complex to S1 while restricting its association with S2, thereby fine tuning the spatial organization of miR-122/Ago2 complexes bound to the viral RNA.
HostingRepository	PRIDE
AnnounceDate	2019-04-24
AnnouncementXML	Submission_2019-04-24_00:30:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Li Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-12 02:48:58	ID requested
⏵ 1	2019-04-24 00:30:28	announced
2	2024-10-22 04:11:45	announced	2024-10-22: Updated project metadata.

Li Y, Wang L, Rivera-Serrano EE, Chen X, Lemon SM, TNRC6 proteins modulate hepatitis C virus replication by spatially regulating the binding of miR-122/Ago2 complexes to viral RNA. Nucleic Acids Res, 47(12):6411-6424(2019) [pubmed]

curator keyword: Biological

submitter keyword: microRNA, RISC complex, protein translation, RNA stability, AP-MS

Stanley M Lemon
contact affiliation	Professor of Medicine, School of Medicine, University of North Carolina at Chapel Hill
contact email	smlemon@med.unc.edu
lab head
Li Wang
contact affiliation	Postdoctoral Research Associate
contact email	liwang@email.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013054
     1. Label: PRIDE project
     2. Name: miR-122-dependent binding of TNRC6 to HCV RNA