Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential by Yongfei Fan, Xinwei Li, Huihui Sun, Zhaojia Gao, Zheng Zhu, Kai Yuan

“…Wilms’ tumor 1-associating protein (WTAP) is required for N⁶-methyladenosine (m⁶A) RNA methylation modifications, which regulate biological processes such as RNA splicing, cell proliferation, cell cycle, and embryonic development. m⁶A is the predominant form of mRNA modification in eukaryotes. …”
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Exon-intron boundary inhibits m6A deposition, enabling m6A distribution hallmark, longer mRNA half-life and flexible protein coding by Zhiyuan Luo, Qilian Ma, Shan Sun, Ningning Li, Hongfeng Wang, Zheng Ying, Shengdong Ke

“…Experiments validate that m6A signal increases once the host gene does not undergo pre-mRNA splicing to produce the same mRNA. Inhibited m6A sites have higher m6A enhancers and lower m6A silencers locally and show high heterogeneity at different exons genome-widely, with only a small proportion (12% to 15%) of exons showing strong inhibition, enabling more stable mRNAs and flexible protein coding. m6A is majorly responsible for why mRNAs with more exons be more stable. …”
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Systems-level proteomics and metabolomics reveals the diel molecular landscape of diverse kale cultivars by Sabine Scandola, Devang Mehta, Brigo Castillo, Nicholas Boyce, R. Glen Uhrig

“…Our results reveal that diel proteome and metabolome signatures divide the selected kale cultivars into two groups defined by their amino acid and sugar content, along with significant proteome differences involving carbon and nitrogen metabolism, mRNA splicing, protein translation and light harvesting. …”
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Overexpression of c-Myc-dependent heterogeneous nuclear ribonucleoprotein A1 promotes proliferation and inhibits apoptosis in NOTCH1-mutated chronic lymphocytic leukemia cells by Yixin Zou, Hanning Tang, Yi Miao, Huayuan Zhu, Li Wang, Lei Fan, Jianxin Fu, Wei Xu, Jianyong Li, Yi Xia, Peng Lyu

“…Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1. Results:. RNA splicing was found to play a vital part in NOTCH1-mutated CLL cells; hence, hnRNPA1 was selected as the focus of this study. …”
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Meta-Analytic Comparison of Global RNA Transcriptomes of Acute and Chronic Myeloid Leukemia Cells Reveals Novel Gene Candidates Governing Myeloid Malignancies by Staša Jurgec, Gregor Jezernik, Mario Gorenjak, Tomaž Büdefeld, Uroš Potočnik

“…GO enrichment analysis showed that DEGs were significantly associated with pre-RNA splicing, reactive oxygen species and glycoprotein metabolism, the cellular endomembrane system, neutrophil migration and antimicrobial immune response. …”
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Mutations in Splicing Factor Genes in Myeloid Malignancies: Significance and Impact on Clinical Features by Valeria Visconte, Megan O. Nakashima, Heesun J. Rogers

“…Components of the pre-messenger RNA splicing machinery are frequently mutated in myeloid malignancies. …”
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The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome. by Senko Tsukuda, James M Harris, Andrea Magri, Peter Balfe, Aleem Siddiqui, Peter A C Wing, Jane A McKeating

“…Mapping the transcription start sites of BCP-RNAs identified a role for hypoxia to regulate pre-genomic RNA splicing that is dependent on m6A modification. Bioinformatic analysis of published single cell RNA-seq of murine liver showed an increased expression of the RNA demethylase ALKBH5 in the peri-central low oxygen region. …”
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Time-course analysis of liver and serum galectin-3 in acute liver injury after alpha-galactosylceramide injection. by Mikiko Matsuo, Ayumu Kanbe, Kei Noguchi, Ayumi Niwa, Yuko Imaizumi, Takahito Kuroda, Koki Ichihashi, Takafumi Okubo, Kosuke Mori, Tomohiro Kanayama, Hiroyuki Tomita, Akira Hara

“…Galectin-3 is a beta-galactoside-binding lectin that plays important roles in diverse physiological functions, such as cell proliferation, apoptosis, and mRNA splicing. This protein is expressed on inflammatory cells and acts as a local inflammatory mediator. …”
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The application of high-throughput proteomics in cytopathology by Ilias P. Nikas, Han Suk Ryu

“…However, the proteins rather than nucleic acids are the functional molecules defining the cellular phenotype in health and disease, whereas genomic profiling cannot evaluate processes such as the RNA splicing or posttranslational modifications and gene expression does not necessarily correlate with protein expression. …”
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Novel <i>PAX9</i> Mutations Causing Isolated Oligodontia by Ye Ji Lee, Yejin Lee, Youn Jung Kim, Zang Hee Lee, Jung-Wook Kim

“…A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5’ splicing site in exon 4. …”
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The Epigenetic Regulation of RNA N6-Methyladenosine Methylation in Glycolipid Metabolism by Haiqing Yang, Yuting Li, Linying Huang, Miaochun Fang, Shun Xu

“…The highly conserved and dynamically reversible N6-methyladenine (m6A) modification has emerged as a critical gene expression regulator by affecting RNA splicing, translation efficiency, and stability at the post-transcriptional level, which has been established to be involved in various physiological and pathological processes, including glycolipid metabolism and the development of glycolipid metabolic disease (GLMD). …”
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Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells. by Mélaine Minville-Walz, Anne-Sophie Pierre, Laurent Pichon, Sandrine Bellenger, Cécile Fèvre, Jérôme Bellenger, Christian Tessier, Michel Narce, Mickaël Rialland

“…In addition, Scd1 depletion induced unfolded protein response (UPR) hallmarks such as Xbp1 mRNA splicing, phosphorylation of eIF2α and increase of CHOP expression. …”
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Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions by Mathieu Courcelles, Christophe Frémin, Laure Voisin, Sébastien Lemieux, Sylvain Meloche, Pierre Thibault

“…Candidate ERK1/2 substrates are involved in diverse cellular processes including transcriptional regulation, chromatin remodeling, RNA splicing, cytoskeleton dynamics, cellular junctions and cell signaling. …”
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NBEAL2 mutations and bleeding in patients with gray platelet syndrome by Fred G. Pluthero, Jorge Di Paola, Manuel D. Carcao, Walter H. A. Kahr

“…Most GPS-associated NBEAL2 mutations generate nonsense codons; frameshifts causing premature translation termination and/or changes in mRNA splicing have also been observed. Data regarding NBEAL2 protein expression in GPS patients is limited. …”
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Antisense Oligonucleotide-Based Rescue of Aberrant Splicing Defects Caused by 15 Pathogenic Variants in <i>ABCA4</i> by Tomasz Z. Tomkiewicz, Nuria Suárez-Herrera, Frans P. M. Cremers, Rob W. J. Collin, Alejandro Garanto

“…The increasing number of variants affecting pre-mRNA splicing makes <i>ABCA4</i> a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. …”
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Context Dependent Sulf1/Sulf2 Functional Divergence in Endothelial Cell Activity by Tiago Justo, Nicola Smart, Gurtej K. Dhoot

“…Exposure of these cells to VEGF-A, TGFβ1, and their inhibitors further highlights their endothelial cell type-specific responses and integral growth factor interactions to regulate cell signalling and selective feedback regulation of HSPG sulfation that additionally exploits alternative Sulf2 RNA-splicing to regulate net VEGF-A and TGFβ cell signalling activities.…”
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Targeting Alternative Splicing as a Potential Therapy for Episodic Ataxia Type 2 by Fanny Jaudon, Simona Baldassari, Ilaria Musante, Agnes Thalhammer, Federico Zara, Lorenzo A. Cingolani

“…Modulating splicing of <i>CACNA1A</i> may therefore represent a promising new strategy to develop improved EA2 therapies. Because RNA splicing is dysregulated in many other genetic diseases, several tools, such as antisense oligonucleotides, <i>trans</i>-splicing, and CRISPR-based strategies, have been developed for medical purposes. …”
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Anticancer and Antiviral Properties of Cardiac Glycosides: A Review to Explore the Mechanism of Actions by Dhanasekhar Reddy, Ranjith Kumavath, Debmalya Barh, Vasco Azevedo, Preetam Ghosh

“…CGs were reported to suppress the HIV-1 gene expression, viral protein translation and alters viral pre-mRNA splicing to inhibit the viral replication. To date, four CGs (Anvirzel, UNBS1450, PBI05204 and digoxin) were in clinical trials for their anticancer activity. …”
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Biallelic HEPHL1 variants impair ferroxidase activity and cause an abnormal hair phenotype. by Prashant Sharma, Marie Reichert, Yan Lu, Thomas C Markello, David R Adams, Peter J Steinbach, Brie K Fuqua, Xenia Parisi, Stephen G Kaler, Christopher D Vulpe, Gregory J Anderson, William A Gahl, May Christine V Malicdan

“…The maternal missense mutation affected mRNA splicing, leading to skipping of exon 5 and causing an in-frame deletion of 85 amino acids (c.809_1063del; p.Leu271_ala355del). …”
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Multiple Phosphorylations of SR Protein SRSF3 and Its Binding to m⁶A Reader YTHDC1 in Human Cells by Takanori Tatsuno, Yasuhito Ishigaki

“…It is also known to regulate mRNA splicing through recruiting SRSF3 to the targeted mRNAs, which then mediates export of YTHDC1-bound RNA to the cytoplasm. …”
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