Rna decay

Oligoadenylate synthetase 3 (OAS3) and ribonuclease L (RNase L) are components of a pathway that combats viral infection in mammals. Upon detection of viral double-stranded RNA (dsRNA), OAS3 synthesizes 2'-5'-oligo(A), which activates the RNase domain of RNase L by promoting the homodimerization and oligomerization of RNase L monomers. Activated RNase L rapidly degrades all cellular mRNAs, shutting off several cellular processes. We sought to understand the molecular mechanisms underlying the rapid activation of RNase L in response to viral infection...

Despite its high effectiveness, combination antiretroviral treatment (cART) has a limited effect on HIV-DNA reservoir, which establishes early during primary infection (PHI) and is maintained by latency, homeostatic T-cells proliferation, and residual replication: this can be associated with low drug exposure in lymphoid tissues and/or suboptimal adherence to antiretroviral drugs (ARVs). Aim of this study was to assess ARVs concentrations in plasma, peripheral blood mononuclear cells (PBMC) and lymph nodes (LN), and their association to HIV-RNA and DNA decay during PHI...

Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous disease characterized by increased iron deposition in the basal ganglia and progressive degeneration of the nervous system in adulthood. However, in early childhood, there were no characteristic features to perform early diagnosis. In our study, a female child exhibited global developmental delay, intellectual disability, and febrile seizure without other distinct clinical phenotypes. Through whole exome sequencing (WES), a de novo nonsense mutation (c...

Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N6 -methyladenosine (m6 A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m6 A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m6 A modification levels. Increasing m6 A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m6 A modification had an opposite effect...

RNA helicases are involved in almost all biological events, and the DDXs family is one of the largest subfamilies of RNA helicases. Recently, studies have reported that RNA helicase DDX21 is involved in several biological events, specifically in orchestrating gene expression. Hence, in this review, we provide a comprehensive overview of the function of DDX21 in health and diseases. In the genome, DDX21 contributes to genome stability by promoting DNA damage repair and resolving R-loops. It also facilitates transcriptional regulation by directly binding to promoter regions, interacting with transcription factors, and enhancing transcription through non-coding RNA...

Hymenochaetales Oberw. is an order classified in Basidiomycota of Fungi, and species in this order display notable diversity. They exhibit various fruiting body shapes, including clavarioid, effused-reflexed, and resupinate basidiomes. Few mycorrhizal species have been reported in Hymenochaetales, but wood-decaying species dominate the order. Hymenochaetaceae Imazeki & Toki and Schizoporaceae Jülich are the most species-rich families within Hymenochaetales, and most species in the Republic of Korea belong to these two families...

1,4-Dioxane concentration in most contaminated water is much less than 1 mg/L, which cannot sustain the growth of most reported 1,4-dioxane-metabolizing pure cultures. These pure cultures were isolated following enrichment of mixed cultures at high concentrations (20 to 1,000 mg/L). This study is based on a different strategy: 1,4-dioxane-metabolizing mixed cultures were enriched by periodically spiking 1,4-dioxane at low concentrations (≤1 mg/L). Five 1,4-dioxane-metabolizing pure strains LCD6B, LCD6D, WC10G, WCD6H, and WD4H were isolated and characterized...

Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein Brain tumor (Brat) promotes degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and in uncommitted intermediate neural progenitors (immature INPs). We identified Ubiquitin-specific protease 5 (Usp5) as a Brat interactor essential for the degradation of Brat target mRNAs in both cell types...

Lipids spontaneously assemble into vesicle-forming membranes. Such vesicles serve as compartments for even the simplest living systems. Vesicles have been extensively studied for constructing synthetic cells or as models for protocells-the cells hypothesized to have existed before life. These compartments exist almost always close to equilibrium. Life, however, exists out of equilibrium. In this work, we studied vesicle-based compartments regulated by a non-equilibrium chemical reaction network that converts activating agents...

Nonsense-mediated mRNA decay (NMD) is a quality-control process that selectively degrades mRNAs having premature termination codon, upstream open reading frame, or unusually long 3'UTR. NMD detects such mRNAs and rapidly degrades them during initial rounds of translation in the eukaryotic cells. Since NMD is a translation-dependent cytoplasmic mRNA surveillance process, the noncoding RNAs were initially believed to be NMD-resistant. The sequence feature-based analysis has revealed that many putative long noncoding RNAs (lncRNAs) have short open reading frames, most of which have translation potential...

The long non-coding RNA X-inactive specific transcript (lncRNA XIST) and MUC1 gene are dysregulated in chronic inflammation and cancer; however, there is no known interaction of their functions. The present studies demonstrate that MUC1-C regulates XIST lncRNA levels by suppressing the RBM15/B, WTAP and METTL3/14 components of the m6A methylation complex that associate with XIST A repeats. MUC1-C also suppresses the YTHDF2-CNOT1 deadenylase complex that recognizes m6A sites and contributes to XIST decay with increases in XIST stability and expression...

Deep learning has emerged as a powerful tool for investigating intricate biological processes in plants by harnessing the potential of large-scale data. Gene regulation is a complex process that transcription factors (TFs), cooperating with their target genes, participate in through various aspects of biological processes. Despite its significance, the study of gene regulation has primarily focused on a limited number of notable instances, leaving numerous aspects and interactions yet to be explored comprehensively...

The most common form of hereditary spastic paraplegia (HSP), SPG4 is caused by single nucleotide variants and microrearrangements in the SPAST gene. The high percentage of multi-exonic deletions or duplications observed in SPG4 patients is predisposed by the presence of a high frequency of Alu sequences in the gene sequence. In the present study, we analyzed DNA and RNA samples collected from patients with different microrearrangements in SPAST to map gene breakpoints and evaluate the mutation mechanism. The study group consisted of 69 individuals, including 50 SPG4 patients and 19 healthy relatives from 18 families...

Staufen-1 (STAU1) is a double-stranded RNA-binding protein (RBP) involved in a variety of pathological conditions. In this study, we investigated the potential role of STAU1 in Alzheimer's disease (AD), in which two hallmarks are well-established as cerebral β-amyloid protein (Aβ) deposition and Tau-centered neurofibrillary tangles. We found that STAU1 protein level was significantly increased in cells that stably express full-length APP and the brain of APP/PS1 mice, an animal model of AD. STAU1 knockdown, as opposed to overexpression, significantly decreased the protein levels of β-amyloid converting enzyme 1 (BACE1) and Aβ...

Objective: Hepatocellular carcinoma (HCC) is a highly lethal cancer with significant mortality, primarily attributed to metastasis. Although Protocadherin Gamma Subfamily A, 9 (PCDHGA9) has been identified as a tumor suppressor gene in cancer metastasis, its role in HCC remains ambiguous. This study aims to clarify the role of PCDHGA9 in HCC by examining its expression, clinical significance, and molecular activities. Methods: Tissue microarray immunofluorescence analysis evaluated the expression of PCDHGA9 and its clinical relevance...

AIMS: This study aims to explore the molecular mechanism of circular RNAs' (circRNAs) potential involvement in myocardial ischaemia-reperfusion injury (MIRI). METHODS AND RESULTS: Differently expressed genes in myocardial infarction (MI) were identified by screening the GEO database. Serum was collected from MI patients and healthy volunteers (n = 5 for each group). AC16 cells were cultured and exposed to hypoxia/reperfusion (H/R) treatment for the cell experiments...

Age-related changes in DNA methylation (DNAm) form the basis of the most robust predictors of age-epigenetic clocks-but a clear mechanistic understanding of exactly which aspects of aging are quantified by these clocks is lacking. Here, to clarify the nature of epigenetic aging, we juxtapose the dynamics of tissue and single-cell DNAm in mice. We compare these changes during early development with those observed during adult aging in mice, and corroborate our analyses with a single-cell RNA sequencing analysis within the same multiomics dataset...

Animal geneticists and breeders have the impending challenge of enhancing the resilience of Indian livestock to heat stress through better selection strategies. Climate change's impact on livestock is more intense in tropical countries like India where dairy cattle crossbreeds are more sensitive to heat stress. The main reason for this study was to find the missing relative changes in transcript levels in thermo-neutral and heat stress conditions in crossbred cattle through whole-transcriptome analysis of RNA-Seq data...

Nonstructural protein 1 (nsp1) of the severe acute respiratory syndrome coronavirus (SCOV1 and SCOV2) acts as a host shutoff protein by blocking the translation of host mRNAs and triggering their decay. Surprisingly, viral RNA, which resembles host mRNAs containing a 5'-cap and a 3'-poly(A) tail, escapes significant translation inhibition and RNA decay, aiding viral propagation. Current literature proposes that, in SCOV2, nsp1 binds the viral RNA leader sequence, and the interaction may serve to distinguish viral RNA from host mRNA...

DNA base damage is a major source of oncogenic mutations and disruption to gene expression. The stalling of RNA polymerase II (RNAP) at sites of DNA damage and the subsequent triggering of repair processes have major roles in shaping the genome-wide distribution of mutations, clearing barriers to transcription, and minimizing the production of miscoded gene products. Despite its importance for genetic integrity, key mechanistic features of this transcription-coupled repair (TCR) process are controversial or unknown...