Dataset Information

Proteome profiling of RNF213 depleted cells reveals nitric oxide regulator DDAH1 antilisterial activity

ABSTRACT: RNF213 is a large, poorly characterized interferon-induced protein. Mutations in RNF213 are associated with predisposition for Moyamoya disease (MMD), a rare cerebrovascular disorder. Recently, RNF213 was found to have broad antimicrobial activity in vitro and in vivo, yet the molecular mechanisms behind this function remain unclear. Using mass spectrometry-based proteomics and validation by real-time PCR we here report that knockdown of RNF213 leads to transcriptional upregulation of MVP and downregulation of CYR61, in line with reported pro- and anti-bacterial activities of these proteins. Knockdown of RNF213 also results in downregulation of DDAH1, which we discover to exert anti-microbial activity against Listeria monocytogenes infection. DDAH1 regulates production nitric oxide (NO), a molecule with both vascular and antimicrobial effects. We show that NO production is reduced in macrophages from RNF213 KO mice, suggesting that RNF213 controls Listeria infection through regulation of DDAH1 transcription and production of NO. Our findings propose a potential mechanism for the antilisterial activity of RNF213 and highlight NO as a potential link between RNF213-mediated immune responses and the development of MMD.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Hela Cell

SUBMITTER: Fabien Thery

LAB HEAD: Francis Impens

PROVIDER: PXD027130 | Pride | 2022-02-17

REPOSITORIES: Pride

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Proteome Profiling of RNF213 Depleted Cells Reveals Nitric Oxide Regulator DDAH1 Antilisterial Activity.

Martina Lia L Asselman Caroline C Thery Fabien F Boucher Katie K Delhaye Louis L Maia Teresa M TM Dermaut Bart B Eyckerman Sven S Impens Francis F

Frontiers in cellular and infection microbiology 20211103

RNF213 is a large, poorly characterized interferon-induced protein. Mutations in RNF213 are associated with predisposition for Moyamoya disease (MMD), a rare cerebrovascular disorder. Recently, RNF213 was found to have broad antimicrobial activity <i>in vitro</i> and <i>in vivo</i>, yet the molecular mechanisms behind this function remain unclear. Using mass spectrometry-based proteomics and validation by real-time PCR we report here that knockdown of RNF213 leads to transcriptional upregulation ...[more]

PMID: 34804992

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	B_KDNT_IFN_32.raw	Raw
	B_KDNT_IFN_33.raw	Raw
	B_KDNT_IFN_34.raw	Raw
	B_KDNT_IFN_35.raw	Raw
	B_KDNT_untreated_11.raw	Raw