CRISPR in cancer biology and therapy

Nature reviews. Cancer, Год журнала: 2022, Номер 22(5), С. 259 - 279

Опубликована: Фев. 22, 2022

Язык: Английский

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Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects

Nature Reviews Genetics, Год журнала: 2022, Номер 24(4), С. 251 - 269

Опубликована: Дек. 16, 2022

Язык: Английский

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Effects of Synonymous Mutations beyond Codon Bias: The Evidence for Adaptive Synonymous Substitutions from Microbial Evolution Experiments

Genome Biology and Evolution, Год журнала: 2021, Номер 13(9)

Опубликована: Июнь 15, 2021

Synonymous mutations are often assumed to be neutral with respect fitness because they do not alter the encoded amino acid and so cannot "seen" by natural selection. Yet a growing body of evidence suggests that synonymous can have effects drive adaptive evolution through their impacts on gene expression protein folding. Here, we review what microbial experiments taught us about contribution adaptation. A survey site-directed mutagenesis reveals distributions for nonsynonymous more similar, especially beneficial mutations, than expected if all were neutral, suggesting should is typically observed. experimental studies where contributed adaptation shows impact range mechanisms including creation illicit RNA polymerase binding sites impacting transcription changes mRNA folding stability modulate translation. We suggest clonal interference in evolving populations may reason play smaller role based observed effects. finish discussing falsely assuming discuss directions future work exploring evolution.

Язык: Английский

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Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1467 - 1467

Опубликована: Июль 2, 2024

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families the human genome, which CYP1, CYP2, and CYP3 are prominent. Beyond drug CYP metabolize endogenous compounds such as lipids, proteins, hormones to maintain physiological homeostasis. Thus, dysregulation CYP450 can lead different endocrine disorders. Moreover, significantly contribute fatty acid cholesterol synthesis, bile biosynthesis, impacting cellular physiology disease pathogenesis. Their diverse functions emphasize their therapeutic potential managing hypercholesterolemia neurodegenerative diseases. Additionally, implicated onset development illnesses cancer, influencing chemotherapy outcomes. Assessment enzyme expression activity aids evaluating liver health state differentiating between diseases, guiding decisions, optimizing efficacy. Understanding roles clinical effect genetic polymorphisms crucial for developing personalized strategies enhancing responses patient populations.

Язык: Английский

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Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(13), С. 4807 - 4807

Опубликована: Июль 7, 2020

The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate limited, recently introduced mutations have potential alter viral fitness. In addition amino acid changes, could affect RNA secondary structure critical life cycle, or interfere with sequences targeted by host miRNAs. We analysed subsets of genomes from isolates around globe show that several introduce changes Watson-Crick pairing, resultant predicted structure. Filtering targets matching miRNAs expressed SARS-CoV-2-permissive cells, we identified ten separate target genome; three these been lost through conserved mutations. A genomic site highly abundant miR-197-5p, overexpressed patients cardiovascular disease, mutation. Our results are compatible model within human constrained miRNA defences. impact further on structures, splice sites offers new context which view future evolution, platform for engineering conditional attenuation vaccine development, as providing better understanding tropism pathogenesis.

Язык: Английский

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The DNA damage sensor ATM kinase interacts with the p53 mRNA and guides the DNA damage response pathway

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Янв. 23, 2024

Abstract Background The ATM kinase constitutes a master regulatory hub of DNA damage and activates the p53 response pathway by phosphorylating MDM2 protein, which develops an affinity for mRNA secondary structure. Disruption this interaction prevents activation nascent p53. link protein— with upstream sensor role in sensing mechanism, are still highly anticipated. Methods proximity ligation assay (PLA) has been extensively used to reveal sub-cellular localisation protein—mRNA protein–protein interactions. ELISA co-immunoprecipitation confirmed interactions vitro cells. Results This study provides novel mechanism whereby interacts enzyme shows that L22L synonymous mutant, known alter structure mRNA, interaction. relevant mechanistic roles Damage Sensing pathway, is linked downstream response, explored. Following (double-stranded breaks activating ATM), activated MDMX protein competes ATM— association NBS1 (MRN complex). These data also binding domains phosphorylation events on regulate trafficking complex cytoplasm. Conclusion presented model describes between pathways; supporting rising functional implications mutations altering structures.

Язык: Английский

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Relative synonymous codon usage and codon pair analysis of depression associated genes

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 12, 2024

Abstract Depression negatively impacts mood, behavior, and mental physical health. It is the third leading cause of suicides worldwide leads to decreased quality life. We examined 18 genes available at genetic testing registry (GTR) from National Center for Biotechnological Information investigate molecular patterns present in depression-associated genes. Different genotypes differential expression are responsible ensuing depression. The study, investigated codon pattern analysis, which might play imperative roles modulating gene Of genes, seven two tended up- down-regulate, respectively, and, remaining different genotypes, an outcome SNPs were alone or combination with conditions associated Codon context analysis revealed abundance identical GTG-GTG CTG-CTG pairs, rarity methionine-initiated pairs. based on usage, preferred codons, rare, be used constructing a deliverable synthetic construct correct level human body, altered depressive state. Other signatures also role evolutionary forces shaping usage.

Язык: Английский

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Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution

npj Precision Oncology, Год журнала: 2025, Номер 9(1)

Опубликована: Янв. 14, 2025

Язык: Английский

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Synonymous mutations promote tumorigenesis by disrupting m6A-dependent mRNA metabolism

Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Synonymous mutations reveal genome-wide levels of positive selection in healthy tissues

Nature Genetics, Год журнала: 2021, Номер 53(11), С. 1597 - 1605

Опубликована: Ноя. 1, 2021

Язык: Английский

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