Small noncoding vault RNA2 ‐1 disrupts gut epithelial barrier function via interaction with HuR

Article28 November 2022 Transparent process Small noncoding vault RNA2-1 disrupts gut epithelial barrier function via interaction with HuR Xiang-Xue Ma Xiang-Xue Ma orcid.org/0000-0001-6556-6812 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Conceptualization, Data curation, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Lan Xiao Lan Xiao Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Conceptualization, Data curation, Software, Formal analysis, Supervision, Validation, Visualization, Methodology Search for more papers by this author Susan J Wen Susan J Wen Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Methodology Search for more papers by this author Ting-Xi Yu Ting-Xi Yu orcid.org/0000-0003-2041-3059 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Visualization, Methodology Search for more papers by this author Shweta Sharma Shweta Sharma orcid.org/0000-0002-6160-1331 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Formal analysis, Validation, Methodology Search for more papers by this author Hee K Chung Hee K Chung Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, ​Investigation, Methodology Search for more papers by this author Bridgette Warner Bridgette Warner orcid.org/0000-0002-0416-6177 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Methodology Search for more papers by this author Caroline G Mallard Caroline G Mallard Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Methodology Search for more papers by this author Jaladanki N Rao Jaladanki N Rao orcid.org/0000-0002-5669-8992 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA Contribution: Conceptualization, Data curation, Validation, ​Investigation, Methodology Search for more papers by this author Myriam Gorospe Myriam Gorospe Laboratory of Genetics and Genomics, National Institute on Aging-IRP, NIH, Baltimore, MD, USA Contribution: Conceptualization, ​Investigation, Writing - review & editing Search for more papers by this author Jian-Ying Wang Corresponding Author Jian-Ying Wang [email protected] orcid.org/0000-0003-3002-1040 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Laboratory of Genetics and Genomics, National Institute on Aging-IRP, NIH, Baltimore, MD, USA Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, ​Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Xiang-Xue Ma Xiang-Xue Ma orcid.org/0000-0001-6556-6812 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Conceptualization, Data curation, Formal analysis, Validation, Visualization, Methodology Search for more papers by this author Lan Xiao Lan Xiao Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Conceptualization, Data curation, Software, Formal analysis, Supervision, Validation, Visualization, Methodology Search for more papers by this author Susan J Wen Susan J Wen Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Methodology Search for more papers by this author Ting-Xi Yu Ting-Xi Yu orcid.org/0000-0003-2041-3059 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Visualization, Methodology Search for more papers by this author Shweta Sharma Shweta Sharma orcid.org/0000-0002-6160-1331 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Formal analysis, Validation, Methodology Search for more papers by this author Hee K Chung Hee K Chung Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, ​Investigation, Methodology Search for more papers by this author Bridgette Warner Bridgette Warner orcid.org/0000-0002-0416-6177 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Methodology Search for more papers by this author Caroline G Mallard Caroline G Mallard Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Data curation, Validation, Methodology Search for more papers by this author Jaladanki N Rao Jaladanki N Rao orcid.org/0000-0002-5669-8992 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA Contribution: Conceptualization, Data curation, Validation, ​Investigation, Methodology Search for more papers by this author Myriam Gorospe Myriam Gorospe Laboratory of Genetics and Genomics, National Institute on Aging-IRP, NIH, Baltimore, MD, USA Contribution: Conceptualization, ​Investigation, Writing - review & editing Search for more papers by this author Jian-Ying Wang Corresponding Author Jian-Ying Wang [email protected] orcid.org/0000-0003-3002-1040 Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA Laboratory of Genetics and Genomics, National Institute on Aging-IRP, NIH, Baltimore, MD, USA Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA Contribution: Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, ​Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Author Information Xiang-Xue Ma1,5,†, Lan Xiao1,†, Susan J Wen1, Ting-Xi Yu1, Shweta Sharma1, Hee K Chung1, Bridgette Warner1, Caroline G Mallard1, Jaladanki N Rao1,2, Myriam Gorospe3 and Jian-Ying Wang *,1,3,4 1Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA 2Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA 3Laboratory of Genetics and Genomics, National Institute on Aging-IRP, NIH, Baltimore, MD, USA 4Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA 5Present address: Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China † These authors contributed equally to this work *Corresponding author. Tel: +1 410 706 1049; Fax: +1 410 706 1051; E-mail: [email protected] EMBO Reports (2023)24:e54925https://doi.org/10.15252/embr.202254925 Full textView the full text of the articlePDFDownload PDF of article text and main figures. Peer ReviewDownload a summary of the editorial decision process including editorial decision letters, reviewer comments and author responses to feedback. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2-1 as a novel regulator of the intestinal barrier via interaction with RNA-binding protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls. Ectopically expressed vtRNA2-1 decreases the levels of intercellular junction (IJ) proteins claudin 1, occludin, and E-cadherin and causes intestinal epithelial barrier dysfunction in vitro, whereas vtRNA2-1 silencing promotes barrier function. Increased vtRNA2-1 also decreases IJs in intestinal organoid, inhibits epithelial renewal, and causes Paneth cell defects ex vivo. Elevating the levels of tissue vtRNA2-1 in the intestinal mucosa increases the vulnerability of the gut barrier to septic stress in mice. vtRNA2-1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thus decreasing their translation. These results indicate that vtRNA2-1 impairs intestinal barrier function by repressing HuR-facilitated translation of claudin 1 and occludin. Synopsis Vault RNAs (vtRNAs) are small noncoding RNAs, and their levels increase in intestinal mucosa from patients with IBD. vtRNA2-1 disrupts intestinal epithelial barrier function by decreasing intercellular junctions via interaction with HuR. vtRNA2-1 inhibits expression of claudin 1, occludin, and E-cadherin posttranscriptionally. vtRNA2-1 impairs intestinal epithelial renewal and causes Paneth cell defects ex vivo. Elevating tissue vtRNA2-1 levels increases vulnerability of gut barrier to septic stress in mice. vtRNA2-1 interacts with HuR and prevents HuR binding to mRNAs. Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 24,Issue 2,06 February 2023This month's cover highlights the article M1AP interacts with the mammalian ZZS complex and promotes male meiotic recombination by Yang Li, Yufan Wu, Ihsan Khan, Hui Ma, Quinghua Shi and colleagues. The microscopic image shows the staining of recombination protein RAD51 (green) and synaptonemal complex lateral element SYCP3 (red) in spread mouse spermatocytes. (Microscopic image copyright Hui Ma and Chenjia Gong, University of Science and Technology of China, Hefei, China.) Volume 24Issue 26 February 2023In this issue ReferencesRelatedDetailsLoading ...