Vault RNA

Non-coding RNAs have been described as crucial regulators of gene expression and guards of cellular homeostasis. Some recent papers focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which makes them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complexes...

Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal nonsyndromic craniosynostosis (sNCS) presenting as the most common CS phenotype. Previous genome-wide association and targeted sequencing analyses of sNCS have identified multiple associated loci, with the strongest association on chromosome 20. Herein, we report the first whole-genome sequencing study of sNCS using 63 proband-parent trios...

Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1-G93A model of ALS. Functional analyses of microglia derived from the lumbar spinal cord of symptomatic mice revealed: (i) remarkably high mitotic index (close to 100% cells are Ki67+) (ii) significant decrease in phagocytic capacity when compared to age-matched control microglia, and (iii) diminished response to innate immune challenges in vitro and in vivo...

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PURPOSE: Vault (vt) RNAs are noncoding (nc) RNAs transcribed by RNA polymerase III (RNA Pol III) with 5'-triphosphate (5'-PPP) termini that play significant roles and are recognized by innate immune sensors, including retinoic acid-inducible protein 1 (RIG-I). In addition, vtRNAs adopt secondary structures that can be targets of interferon-inducible protein kinase R (PKR) and the oligoadenylate synthetase (OAS)/RNase L system, both of which are important for activating antiviral defenses...

Non-coding RNAs (ncRNAs) are highly plastic RNA molecules that can sequester cellular proteins and other RNAs, serve as transporters of cellular cargo and provide spatiotemporal feedback to the genome. Mounting evidence indicates that ncRNAs are central to biology, and are critical for neuronal development, metabolism and intra- and intercellular communication in the brain. Their plasticity arises from state-dependent dynamic structure states that can be influenced by cell type and subcellular environment, which can subsequently enable the same ncRNA with discrete functions in different contexts...

RNA caps are deposited at the 5'end of RNA-polymerase II transcripts. This modification regulates several steps of gene expression, in addition to marking transcripts as self to enable the innate immune system to distinguish them from uncapped foreign RNAs, including those derived from viruses. Specialized immune sensors, such as RIG-I and IFITs, trigger antiviral responses upon recognition of uncapped cytoplasmic transcripts. Interestingly, uncapped transcripts can also be produced by mammalian hosts. For instance, 5'-triphosphate RNAs are generated by RNA-polymerase III transcription, including tRNAs, Alu RNAs, or vault RNAs...

The human intestinal epithelium has an impressive ability to respond to insults and its homeostasis is maintained by well-regulated mechanisms under various pathophysiological conditions. Nonetheless, acute injury and inhibited regeneration of the intestinal epithelium occur commonly in critically ill surgical patients, leading to the translocation of luminal toxic substances and bacteria to the bloodstream. Effective therapies for the preservation of intestinal epithelial integrity and for the prevention of mucosal hemorrhage and gut barrier dysfunction are limited, primarily because of a poor understanding of the mechanisms underlying mucosal disruption...

RNA viruses have been shown to express various short RNAs, some of which have regulatory roles during replication, transcription, and translation of viral genomes. However, short viral RNAs generated from SARS-CoV-1 and SARS-CoV-2 genomic RNAs remained largely unexplored, possibly due limitations of the widely used library preparation methods for small RNA deep sequencing and corresponding data processing. By analyzing publicly available small RNA sequencing datasets, we observed that human Calu-3 cells infected by SARS-CoV-1 or SARS-CoV-2 accumulate multiple previously unreported short viral RNAs...

PARP4 is an ADP-ribosyltransferase that resides within the vault ribonucleoprotein organelle. Our knowledge of PARP4 structure and biochemistry is limited relative to other PARPs. PARP4 shares a region of homology with PARP1, an ADP-ribosyltransferase that produces poly(ADP-ribose) from NAD+ in response to binding DNA breaks. The PARP1-homology region of PARP4 includes a BRCT fold, a WGR domain, and the catalytic (CAT) domain. Here, we have determined X-ray structures of the PARP4 catalytic domain and performed biochemical analysis that together indicate an active site that is open to NAD+ interaction, in contrast to the closed conformation of the PARP1 catalytic domain that blocks access to substrate NAD+...

The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body and its homeostasis is tightly controlled by numerous factors at multiple levels. The RNA-binding protein HuR (human antigen R) is intimately involved in many aspects of gut mucosal pathobiology and plays an important role in maintaining integrity of the intestinal epithelium by regulating stability and translation of target mRNAs. Nonetheless, deregulation of HuR expression and altered binding affinity of HuR for target transcripts occur commonly in various gut mucosal disorders...

SQSTM1/p62 bodies are phase-separated condensates that play a fundamental role in intracellular quality control and stress responses. Despite extensive studies investigating the mechanism of formation and degradation of SQSTM1/p62 bodies, the constituents of SQSTM1/p62 bodies remain elusive. We recently developed a purification method for intracellular SQSTM1/p62 bodies using a cell sorter and identified their constituents by mass spectrometry. Combined with mass spectrometry of tissues from selective autophagy-deficient mice, we identified vault, a ubiquitous non-membranous organelle composed of proteins and non-coding RNA, as a novel substrate for selective autophagy...

The physicochemical characteristics of RNA admit non-coding RNAs to perform a different range of biological acts through various mechanisms and are involved in regulating a diversity of fundamental processes. Notably, some reports of pathological conditions have proved abnormal expression of many non-coding RNAs guides the ailment. Vault RNAs are a class of non-coding RNAs containing stem regions or loops with well-conserved sequence patterns that play a fundamental role in the function of vault particles through RNA-ligand, RNA-RNA, or RNA-protein interactions...

Recent advancements in small RNA sequencing have unveiled a previously hidden world of regulatory small non-coding RNAs (sncRNAs) that extend beyond the well-studied siRNAs, miRNAs, and piRNAs. This exploration, starting with tRNA-derived small RNAs (tsRNAs), has led to the discovery of a diverse universe of sncRNAs derived from various structured RNAs such as rRNAs, snoRNAs, snRNAs, Y RNAs, and Vault RNAs, with exciting uncharted functional possibilities. In this perspective, we discuss the emerging functional principles of sncRNAs beyond the well-known RNAi-like mechanisms, focusing on those that operate independent of linear sequence complementarity but rather function in an aptamer-like fashion...

Among extracellular non‑coding RNAs, serum levels of microRNAs have been extensively investigated in cancers. In contrast, the serum levels of vault RNAs (vtRNAs) in relation to various disease conditions remain poorly understood. The present study evaluated the clinical significance of serum vtRNA1‑1 levels in patients with blood diseases. The stability and sub‑localisation of serum vtRNA1‑1 was assessed and a reverse transcription‑quantitative PCR method using spiked RNA to quantify serum vtRNA1‑1 was developed...

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis and the role of IL-6 in pathogenesis is becoming increasingly important. A recent whole genome DNA methylation screening in IgAN patients identified a hypermethylated region comprising the non-coding RNA Vault RNA 2-1 (VTRNA2-1) that could explain the high IL-6 levels. METHODS: The pathway leading to IL-6 secretion controlled by VTRNA2-1, PKR, and CREB was analyzed in peripheral blood mononuclear cells (PBMCs) isolated from healthy subjects (HS), IgAN patients, transplanted patients with or without IgAN...

AIMS: To identify differential expression of shorter non-coding RNA (ncRNA) genes associated with autism spectrum disorders (ASD). BACKGROUND: ncRNA are functional molecules that derive from non-translated DNA sequence. The HUGO Gene Nomenclature Committee (HGNC) have approved ncRNA gene classes with alignment to the reference human genome. One subset is microRNA (miRNA), which are highly conserved, short RNA molecules that regulate gene expression by direct post-transcriptional repression of messenger RNA...

OBJECTIVE: To expand in an unbiased manner our knowledge of autoantigens and autoantibodies in patients with systemic lupus erythematosus (SLE) and evaluate their associations with serological and clinical parameters. METHODS: Human proteome arrays (>21,000 proteins) were screened with serum from SLE patients (n=12) and healthy controls (n=6) for IgG and IgA binding. Top hits were validated with two cohorts of SLE patients (n=49, n=46) and other rheumatic diseases by ELISA...

Gene expression can be regulated by transcriptional or post-transcriptional gene silencing. Recently, we described nuclear nascent RNA silencing that is mediated by Dicer-dependent tRNA-derived small RNA molecules. In addition to tRNA, RNA polymerase III also transcribes vault RNA, a component of the ribonucleoprotein complex vault. Here, we show that Dicer-dependent small vault RNA1-2 (svtRNA1-2) associates with Argonaute 2 (Ago2). Although endogenous vtRNA1-2 is present mostly in the cytoplasm, svtRNA1-2 localises predominantly in the nucleus...

Cancers display dynamic interactions with their complex microenvironments that influence tumor growth, invasiveness, and immune evasion, thereby also influencing potential resistance to therapeutic treatments. The tumor microenvironment (TME) includes cells of the immune system, the extracellular matrix, blood vessels, and other cell types, such as fibroblasts or adipocytes. Various cell types forming this TME secrete exosomes, and molecules thereby released into the TME have been shown to be important mediators of cellular communication and interplay...