Roles of Small Noncoding Vault RNAs in Intestinal Epithelium Homeostasis and Diseases

The mammalian intestinal epithelium is a rapid self-renewing tissue that functions as a physical barrier against a wide array of noxious substances and the gut microbiome that inhabit the intestinal lumen. Homeostasis of the intestinal epithelium is tightly regulated via well-controlled mechanisms and depends on rapid gene expression pattern alterations to effectively regulate cell survival, adapt to stress, and keep epithelial integrity in stressful environments. Vault RNAs (vtRNAs) are small noncoding RNAs that are highly expressed in the intestinal epithelium and involved in many cellular processes essential for healthy and pathological states. In this review, we provide a broad discussion of vtRNA biogenesis, the roles of vtRNAs in intestinal mucosal renewal and gut barrier function regulation, and the interactions of vtRNAs with RNA-binding proteins in modulating mRNA stability and translation. We also highlight the implications of vtRNAs in human gut mucosal disorders and point out vtRNAs as potential biomarkers and/or novel targets for developing new diagnostic and/or therapeutic modalities for identifying and preserving the integrity of the intestinal epithelial lining in patients with critical disorders.