Oxidized polyunsaturated fatty acid promotes colitis and colitis-associated tumorigenesis in mice.

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.

Variable calling of m6A and associated features in databases: a guide for end-users.

N6-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.

Pan-Cancer Analysis Links Altered RNA mG Methyltransferase Expression to Oncogenic Pathways, Immune Cell Infiltrations and Overall Survival.

Background: 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.

Interplay between N-adenosine RNA methylation and mRNA splicing.

N-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.

Dynamic changes in RNA mA and 5 hmC influence gene expression programs during macrophage differentiation and polarisation.

RNA 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.

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy.

The 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.

A multiomics dataset for the study of RNA modifications in human macrophage differentiation and polarisation.

RNA 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.

Zebrafish and increase susceptibility to mycobacterial infection.

Regulation 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.

Ku70 senses cytosolic DNA and assembles a tumor-suppressive signalosome.

The 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.

SpliceWiz: interactive analysis and visualization of alternative splicing in R.

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.

CYP eicosanoid pathway mediates colon cancer-promoting effects of dietary linoleic acid.

Human 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.

Overexpression of VIRMA confers vulnerability to breast cancers via the mA-dependent regulation of unfolded protein response.

Virilizer-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.

MLH1-methylated endometrial cancer under 60 years of age as the "sentinel" cancer in female carriers of high-risk constitutional MLH1 epimutation.

Objective: 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.

The N6-methyladenosine RNA landscape in the aged mouse hippocampus.

The 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.

OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection.

Pathogenic 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.

Intron retention: importance, challenges, and opportunities.

Recent 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.

The multifaceted effects of YTHDC1-mediated nuclear mA recognition.

N6-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.

Dynamic intron retention modulates gene expression in the monocytic differentiation pathway.

Monocytes 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).

Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting.

PDCD10, also known as CCM3, is a gene found to be associated with the human disease cerebral cavernous malformations (CCMs). PDCD10 forms a complex with GCKIII kinases including STK24, STK25, and MST4. Studies in C.

The mA-epitranscriptome in brain plasticity, learning and memory.

Activity-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.

CCM2L (Cerebral Cavernous Malformation 2 Like) Deletion Aggravates Cerebral Cavernous Malformation Through Map3k3-KLF Signaling Pathway.

[Figure: see text].

Widespread Aberrant Alternative Splicing despite Molecular Remission in Chronic Myeloid Leukaemia Patients.

Vast transcriptomics and epigenomics changes are characteristic of human cancers, including leukaemia. At remission, we assume that these changes normalise so that omics-profiles resemble those of healthy individuals. However, an in-depth transcriptomic and epigenomic analysis of cancer remission has not been undertaken.