Involvement of Cryptosporidium parvum Cdg7_FLc_1000 RNA in the Attenuation of Intestinal Epithelial Cell Migration via Trans-Suppression of Host Cell SMPD3. (7th August 2017)

• Record Type: Journal Article
• Authors: Ming, Zhenping; Gong, Ai-Yu; Wang, Yang; Zhang, Xin-Tian; Li, Min; Mathy, Nicholas W; Strauss-Soukup, Juliane K; Chen, Xian-Ming
• Is Part Of: Journal of infectious diseases. Volume 217:Number 1(2018)
• Page Start: 122
• Page End: 133
• Publication Date: 2017-08-07
• Subjects: Cryptosporidium -- cryptosporidiosis -- intestinal epithelium -- parasitic infection -- SMPD3 -- gene transcription -- cell migration; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix392
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Infection by Cryptosporidium parvum causes inhibition of intestinal epithelial turnover, but underlying mechanisms are unclear. This study indicates that parasite Cdg7_Flc_1000 RNA is delivered into host cells during infection, attenuating epithelial cell migration through suppression of host SMPD3 . Abstract: Intestinal infection by Cryptosporidium parvum causes inhibition of epithelial turnover, but underlying mechanisms are unclear. Previous studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected epithelial cells. Using in vitro and in vivo models of intestinal cryptosporidiosis, we report here that host delivery of parasite Cdg7_FLc_1000 RNA results in inhibition of epithelial cell migration through suppression of the gene encoding sphingomyelinase 3 ( SMPD3 ). Delivery of Cdg7_FLc_1000 into infected cells promotes the histone methyltransferase G9a–mediated H3K9 methylation in the SMPD3 locus. The DNA-binding transcriptional repressor, PR domain zinc finger protein 1, is required for the assembly of Cdg7_FLc_1000 into the G9a complex and associated with the enrichment of H3K9 methylation at the gene locus. Pathologically, nuclear transfer of Cryptosporidium parvum Cdg7_FLc_1000 RNA is involved in the attenuation of intestinal epithelial cell migration via trans-suppression of host cell SMPD3 .