TL;DR
This review article scrutinizes the aberrations in RNA splicing linked to cancer and explores therapeutic endeavors directed at addressing mutations in RNA splicing.
This review integrates the molecular logic of splice-site selection with the cancer-specific mechanisms that perturb it, summarizes representative isoform switches across the hallmarks of cancer, evaluates emerging technologies and clinical biomarkers, and discusses the opportunities and constraints of translating spli...
This review describes how spliceosome assembly, splicing regulatory elements, splicing factors, epigenetic modifications, and post-transcriptional processes determine splice-site selection and suggests that safe clinical translation will require greater selectivity, reduced off-target toxicity, and preservation of esse...
Progress will require more selective splicing-directed modalities, pharmacodynamic biomarkers that measure splicing perturbation in the relevant tumor or blood compartment, longitudinal mapping of genetic and tumor cell-state plasticity-driven resistance, and biomarker-defined combination trials to support expansion fr...
Aging is characterized by progressive loss of molecular fidelity that compromises stem-cell function and tissue homeostasis. Aging transcriptomes show widespread disruption of RNA processing, including increased intron retention, cryptic splice-site usage, and altered RNA quality control. These changes arise from somat...
Alternative splicing of RNA is a highly regulated process that increases the complexity of gene expression, with disruption of splicing leading to significant disruption of cellular function and, ultimately, disease. This spliceopathy is exemplified by myotonic dystrophy type 1, a CTG repeat expansion disease, where dy...
Endogenous RNA molecules called natural antisense transcripts (NATs) are produced from the complementary DNA strand of either non-coding or protein-coding genes. NATs are not byproducts of random transcription but rather important controllers of gene expression, according to mounting evidence. Antisense transcription h...
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