Splicing of pre-mRNA is one of the post-transcriptional modifications in which introns are removed from primary transcript and exons are joined. pre-mRNA splicing reactions are catalyzed by dynamic complex called spliceosome. Exons can be joined on different manners in a process known as alternative splicing, that provide production of multiple mRNA and protein isoforms from relatively low number of genes. Alternative splicing is regulated by cis elements localized within exons or introns and trans-acting factors including spliceosome components and members of the SR and hnRNP protein family that exert antagonistic effects on splicing. Aberrant pre-mRNA splicing may be caused by mutations in cis elements and altered expression of splicing factors. This review describes disturbances in splicing of genes controlling proliferation and metastasis that can lead to tumoral transformation. Also, potential applications of abnormally spliced transcripts that may potentially serve as diagnostic biomarkers of cancer or targets in anticancer therapy are discussed.
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Int J Mol Sci
March 2025
State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China.
Adrenergic signaling is critical for maintaining cardiac function and works by regulating heart rate, contractility, and stress responses. Protein arginine methyltransferase 5 (PRMT5), a key enzyme involved in gene expression, signal transduction, and RNA processing, has been revealed to be an important factor in heart disease. However, its specific effects on adrenergic signaling have not been fully elucidated.
View Article and Find Full Text PDFInt J Mol Sci
March 2025
Department of Pediatrics, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan.
Since 2016, splice-switching therapy, in which splicing is controlled by antisense oligonucleotides, has been applied in clinical practice for spinal muscular atrophy and Duchenne muscular dystrophy. In the former disease, this therapy induces exon inclusion, while, in the latter, it induces exon skipping, leading expression of functional proteins. Basic and clinical studies of splice-switching therapy for many monogenic diseases have now been conducted.
View Article and Find Full Text PDFInt J Mol Sci
February 2025
Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria.
The premature aging disease Hutchinson-Gilford Syndrome (HGPS) is caused by defined mutations in the LMNA gene, resulting in the activation of a cryptic splice donor site, which leads to a defective truncated prelamin A protein called progerin. Notably, progerin expression has also been detected in non-mutated healthy individuals, and therefore, its involvement in the physiological aging process has been widely discussed. Since diabetes mellitus is associated with premature aging and increased cardiovascular mortality, we aimed to investigate the role of progerin expression in patients with diabetic retinopathy (DR).
View Article and Find Full Text PDFMol Genet Genomics
March 2025
Department of Thoracic Oncology, Tongji Medical College, Hubei Cancer Hospital, Huazhong University of Science and Technology, No. 116 Zhuodaoquan South Rd, Wuhan, Hubei, 430079, China.
Our study aimed to explore how DEK, a carcinogenic protein with chromatin architectural function, genome-widely binds to RNA and affects the alternative splicing in cancer cells to decipher its molecular functions. To achieve this goal, cell phenotype experiments, RNA sequencing (RNA-seq), and improved RNA immunoprecipitation sequencing (iRIP-seq) were conducted to identify the function and regulated targets of DEK in HeLa cells. The results showed DEK overexpression promoted cell proliferation and invasion of HeLa cells.
View Article and Find Full Text PDFCell Mol Life Sci
March 2025
Faculty of Medicine, Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, University of Cologne, Cologne, Germany.
Background: Esophageal adenocarcinomas (EACs) represent an evolving tumor entity with high mortality rates. MET amplification is a recurrent driver in EACs and is associated with decreased patient survival. However, the response to MET inhibitors is limited.
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