Small and long non-coding RNAs: Past, present, and future

Cell, Год журнала: 2024, Номер 187(23), С. 6451 - 6485

Опубликована: Ноя. 1, 2024

Язык: Английский

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Structural Features of 5′ Untranslated Region in Translational Control of Eukaryotes

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1979 - 1979

Опубликована: Фев. 25, 2025

Gene expression is a complex process regulated at multiple levels in eukaryotic cells. Translation frequently represents pivotal step the control of gene expression. Among stages translation, initiation particularly important, as it governs ribosome recruitment and efficiency protein synthesis. The 5' untranslated region (5' UTR) mRNA plays key role this process, often exhibiting complicated structured landscape. Numerous mRNAs possess long UTRs that contain diverse regulatory elements, including RNA secondary structures, specific nucleotide motifs, chemical modifications. These structural features can independently modulate translation through their intrinsic properties or by serving platforms for trans-acting factors such RNA-binding proteins. dynamic nature UTR elements allows cells to fine-tune response environmental cellular signals. Understanding these mechanisms not only fundamental molecular biology but also holds significant biomedical potential. Insights into UTR-mediated regulation could drive advancements synthetic mRNA-based targeted therapies. This review outlines current knowledge UTR, interplay between them, combined functional impact on translation.

Язык: Английский

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3’UTR RNA editing driven by ADAR1 modulates MDM2 expression in breast cancer cells

Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)

Опубликована: Май 17, 2025

Язык: Английский

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An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Май 26, 2025

Custom RNA base editing exploiting the human Adenosine Deaminase Acting on (ADAR) enzyme may enable therapeutic gene without DNA damage or use of foreign proteins. ADAR's adenosine-to-inosine (effectively A-to-G) deamination activity can be targeted to transcripts using an antisense guide (gRNA), but efficacy is challenged by limits in vivo delivery. Embedding gRNAs into a U7 small nuclear (snRNA) framework greatly enhances with endogenous ADAR, and 750-plex single-cell mutagenesis screen further improved framework. An optimized scaffold stronger synthetic promoter enables 76% vitro from single construct per cell, 75% Hurler syndrome mouse brain after one systemic AAV injection, surpassing circular gRNA approaches. The technology also improves published DMD exon-skipping designs 25-fold differentiated myoblasts. Our engineered represents universal for ADAR-based other therapies.

Язык: Английский

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Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus

RNA Biology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 4, 2025

Adenosine-to-inosine (A-to-I) RNA editing, catalysed by two ADAR isoforms (p110 and p150) ADARB1, is a critical regulatory step in gene expression. Intriguingly, the nucleolus conspicuously rich p110 though biological reason remains unclear. To investigate putative role of nucleolar enrichment ADAR, we released it gradually from into nucleoplasm treating cells briefly with low doses actinomycin D, known to disassemble nucleolus. Deep sequencing transcriptome revealed that as dissociated nucleolus, editing increased significantly, sharp rises both number edited sites frequency. This co-transcriptional predominantly intronic regions, was associated disrupted pre-mRNA splicing, causing exon skipping intron retention which remodelled These findings suggest localization serves restrain its activity, preventing excessive could lead splicing errors cellular dysfunction.

Язык: Английский

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Suppression of double-stranded RNA sensing in cancer: molecular mechanisms and therapeutic potential

Biochemical Society Transactions, Год журнала: 2024, Номер unknown

Опубликована: Сен. 2, 2024

Immunotherapy has emerged as a therapeutic option for many cancers. For some tumors, immune checkpoint inhibitors show great efficacy in promoting anti-tumor immunity. However, not all tumors respond to immunotherapies. These often exhibit reduced inflammation and are resistant inhibitors. Therapies that turn these ‘cold’ ‘hot’ could improve the applicability of inhibitors, cases may be sufficient on their own promote One strategy accomplish this goal is activate innate immunity pathways within tumor. Here we describe how can accomplished by activating double-stranded RNA (dsRNA) sensors. sensors evolved detect dsRNAs arising from viral infection but also activated endogenous dsRNAs. A set proteins, referred suppressors dsRNA sensing, responsible preventing sensing ‘self’ pathways. The mechanism action falls into three categories: (1) Suppressors affect mature RNAs through editing, degradation, restructuring, or binding. (2) processing. (3) expression. In review highlight function each mechanism, provide examples effects disrupting those cancer cell lines discuss potential targeting proteins

Язык: Английский

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The mechanism of discriminative aminoacylation by isoleucyl-tRNA synthetase based on wobble nucleotide recognition

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 30, 2024

The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity protein translation. Isoleucyl-tRNA synthetase (IleRS) distinguishes tRNA

Язык: Английский

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