Background And Aims: Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD.
View Article and Find Full Text PDFN6-methyladenosine (m$^{6}$A) is a widely-studied methylation to messenger RNAs, which has been linked to diverse cellular processes and human diseases. Numerous databases that collate m$^{6}$A profiles of distinct cell types have been created to facilitate quick and easy mining of m$^{6}$A signatures associated with cell-specific phenotypes. However, these databases contain inherent complexities that have not been explicitly reported, which may lead to inaccurate identification and interpretation of m$^{6}$A-associated biology by end-users who are unaware of them.
View Article and Find Full Text PDFBackground: N7-methylguanosine (mG) modification is one of the most prevalent RNA modifications in humans. Dysregulated mG modifications caused by aberrant expression of mG writers contribute to cancer progression and result in worse patient survival in several human cancers. However, studies that systematically assess the frequency and clinical relevance of aberrant mG writer expression in a pan-cancer cohort remain to be performed.
View Article and Find Full Text PDFN-methyladenosine (mA) is the most abundant modification to mRNAs. Loss-of-function studies of main mA regulators have indicated the role of mA in pre-mRNA splicing. Recent studies have reported the role of splicing in preventing mA deposition.
View Article and Find Full Text PDFRNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications regulate the innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. While mA has been widely studied, other RNA modifications, including 5 hmC, remain poorly characterised.
View Article and Find Full Text PDFThe N6-methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising RNA methylation have been identified. Notably, these m6A regulators often exhibit altered expression patterns in cancer, occasionally offering prognostic value.
View Article and Find Full Text PDFRNA modifications have emerged as central regulators of gene expression programs. Amongst RNA modifications are N6-methyladenosine (mA) and RNA 5-hydroxymethylcytosine (5hmC). While mA is established as a versatile regulator of RNA metabolism, the functions of RNA 5hmC are unclear.
View Article and Find Full Text PDFRegulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish- infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways.
View Article and Find Full Text PDFThe innate immune response contributes to the development or attenuation of acute and chronic diseases, including cancer. Microbial DNA and mislocalized DNA from damaged host cells can activate different host responses that shape disease outcomes. Here, we show that mice and humans lacking a single allele of the DNA repair protein Ku70 had increased susceptibility to the development of intestinal cancer.
View Article and Find Full Text PDFBrief Bioinform
November 2023
Alternative splicing (AS) is a crucial mechanism for regulating gene expression and isoform diversity in eukaryotes. However, the analysis and visualization of AS events from RNA sequencing data remains challenging. Most tools require a certain level of computer literacy and the available means of visualizing AS events, such as coverage and sashimi plots, have limitations and can be misleading.
View Article and Find Full Text PDFHuman and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω-6), an essential fatty acid and key component of the human diet, increases the risk of colon cancer. However, results from human studies have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given the importance of LA in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer-promoting effects.
View Article and Find Full Text PDFVirilizer-like mA methyltransferase-associated protein (VIRMA) maintains the stability of the mA writer complex. Although VIRMA is critical for RNA mA deposition, the impact of aberrant VIRMA expression in human diseases remains unclear. We show that VIRMA is amplified and overexpressed in 15-20% of breast cancers.
View Article and Find Full Text PDFObjective: Universal screening of endometrial carcinoma (EC) for mismatch repair deficiency (MMRd) and Lynch syndrome uses presence of MLH1 methylation to omit common sporadic cases from follow-up germline testing. However, this overlooks rare cases with high-risk constitutional MLH1 methylation (epimutation), a poorly-recognized mechanism that predisposes to Lynch-type cancers with MLH1 methylation. We aimed to determine the role and frequency of constitutional MLH1 methylation among EC cases with MMRd, MLH1-methylated tumors.
View Article and Find Full Text PDFBreast Cancer Res
December 2022
Background: After many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR, and such patterns have been pursued as both biomarkers and therapeutic targets. Paradoxically, breast cancer (BrCa) is the only tumour type in which IR is reduced compared to adjacent normal breast tissue.
View Article and Find Full Text PDFThe aged brain is associated with an inevitable decline in cognitive function and increased vulnerability to neurodegenerative disorders. Multiple molecular hallmarks have been associated with the aging nervous system through transcriptomics and proteomic studies. Recently, epitranscriptomic analysis has highlighted the role of RNA chemical modification in various biological processes.
View Article and Find Full Text PDFPathogenic mycobacteria inhibit inflammasome activation to establish infection. Although it is known that potassium efflux is a trigger for inflammasome activation, the interaction between mycobacterial infection, potassium efflux, and inflammasome activation has not been investigated. Here, we use infection of zebrafish embryos and infection of THP-1 cells to demonstrate that pathogenic mycobacteria up-regulate the host WNK signalling pathway kinases SPAK and OXSR1 which control intracellular potassium balance.
View Article and Find Full Text PDFRecent landmark discoveries have underpinned the physiological importance of intron retention (IR) across multiple domains of life and revealed an unexpected breath of functions in a large variety of biological processes. Despite significant progress in the field, some challenges remain. Once solved, opportunities will arise for discovering more functions of IR.
View Article and Find Full Text PDFN6-methyladenosine or mA modification to mRNAs is now recognised as a key regulator of gene expression and protein translation. The fate of mA-modified mRNAs is decoded by mA readers, mostly found in the cytoplasm, except for the nuclear-localised YTHDC1. While earlier studies have implicated YTHDC1-mA functions in alternative splicing and mRNA export, recent literature has expanded its close association to the chromatin-associated, noncoding and regulatory RNAs to fine-tune transcription and gene expression in cells.
View Article and Find Full Text PDFMonocytes play a crucial role in maintaining homeostasis and mediating a successful innate immune response. They also act as central players in diverse pathological conditions, thus making them an attractive therapeutic target. Within the bone marrow, monocytes arise from a committed precursor termed Common Monocyte Progenitor (cMoP).
View Article and Find Full Text PDFVascular smooth muscle cells (VSMCs) display extraordinary phenotypic plasticity. This allows them to differentiate or dedifferentiate, depending on environmental cues. The ability to 'switch' between a quiescent contractile phenotype to a highly proliferative synthetic state renders VSMCs as primary mediators of vascular repair and remodelling.
View Article and Find Full Text PDFActivity-dependent gene expression and protein translation underlie the ability of neurons to dynamically adjust their synaptic strength in response to sensory experience and during learning. The emerging field of epitranscriptomics (RNA modifications) has rapidly shifted our views on the mechanisms that regulate gene expression. Among hundreds of biochemical modifications on RNA, N-methyladenosine (mA) is the most abundant reversible mRNA modification in the brain.
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