C2H2-zinc-finger transcription factors bind RNA and function in diverse post-transcriptional regulatory processes

Molecular Cell, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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An RNA-centric view of transcription and genome organization

Molecular Cell, Год журнала: 2024, Номер 84(19), С. 3627 - 3643

Опубликована: Окт. 1, 2024

Язык: Английский

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NesT-NABind: a Nested Transformer for Nucleic Acid-Binding Site Prediction on Protein Surface

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Protein-nucleic acid interactions play a crucial role in many physiological processes. Identifying the binding sites of nucleotides on protein surface is prerequisite for understanding molecular recognition mechanisms between two types macromolecules and also provides information to design or generate molecule modulators against these manipulate biological function according specific requirements. Existing studies mainly focus characterizing local surfaces around sites, often neglecting interrelationships among global information. To address this gap, we propose NesT-NABind, Nested Transformer Nucleic Acid-Binding site prediction. This model leverages Transformer's advanced capabilities contextual long-range dependency capturing. Specifically, introduce patch-scale process each protein-scale transformer integrate sequence entire protein. These Transformers operate at different scales protein, hence term "nested". Experiments demonstrate that NesT-NABind achieves 5.57% improvement F1 score 3.64% AUPRC compared state-of-the-art methods. With incorporation features, shows an enhanced predictive capability challenging large proteins therefore can be used much wider range applications.

Язык: Английский

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Functional screen identifies RBM42 as a mediator of oncogenic mRNA translation specificity

Nature Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Язык: Английский

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Viral influencers: deciphering the role of endogenous retroviral LTR12 repeats in cellular gene expression

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

The human genome is like a museum of ancient retroviral infections. It contains large number endogenous retroviruses (ERVs) that bear witness to past integration events. About 5,000 them are so-called long terminal repeat 12 (LTR12) elements. Compared with 20,000 genes, this remarkable number. Although LTR12 elements can act as promoters or enhancers cellular the function most these has remained unclear. In our mini-review, we show different share many similarities, including common transcription factor binding sites. Furthermore, summarize novel insights into epigenetic mechanisms governing their silencing and activation. Specific examples genes pathways regulated by loci used illustrate regulatory network built repetitive A particular focus on role in regulation antiviral immune responses, tumor cell proliferation, senescence. Finally, describe how targeted activation fascinating ERV family could be for diagnostic therapeutic purposes.

Язык: Английский

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Multi-locus CRISPRi targeting with a single truncated guide RNA

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

Опубликована: Фев. 4, 2025

Язык: Английский

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scPRINT: pre-training on 50 million cells allows robust gene network predictions

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

Опубликована: Апрель 16, 2025

Abstract A cell is governed by the interaction of myriads macromolecules. Inferring such a network interactions has remained an elusive milestone in cellular biology. Building on recent advances large foundation models and their ability to learn without supervision, we present scPRINT, model for inference gene networks pre-trained more than 50 million cells from cellxgene database. Using innovative pretraining tasks architecture, scPRINT pushes transformer towards interpretability usability when uncovering complex biology cell. Based our atlas-level benchmarks, demonstrates superior performance state art, as well competitive zero-shot abilities denoising, batch effect correction, label prediction. On atlas benign prostatic hyperplasia, highlights profound connections between ion exchange, senescence, chronic inflammation.

Язык: Английский

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Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation

Cancer Cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Circular RNA (circRNA) is a class of noncoding with regulatory potentials. Its role in the transdifferentiation prostate and lung adenocarcinoma into neuroendocrine cancer (NEPC) small cell (SCLC) remains unexplored. Here, we identified circRMST as an exceptionally abundant circRNA predominantly expressed NEPC SCLC, strong conservation between humans mice. Functional studies using shRNA, siRNA, CRISPR-Cas13, Cas9 consistently demonstrate that essential for tumor growth expression ASCL1, master regulator fate. Genetic knockout Rmst genetic engineered mouse models prevents transdifferentiation, maintaining tumors state. Mechanistically, physically interacts lineage transcription factors NKX2-1 SOX2. Loss induces protein degradation through autophagy-lysosomal pathway alters genomic binding SOX2, collectively leading to loss ASCL1 transcription.

Язык: Английский

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Transcription factor condensates and signaling driven transcription

Nucleus, Год журнала: 2023, Номер 14(1)

Опубликована: Май 2, 2023

Transcription Factor (TF) condensates are a heterogenous mix of RNA, DNA, and multiple co-factor proteins capable modulating the transcriptional response cell. The dynamic nature spatial location TF-condensates in 3D nuclear space is believed to provide fast response, which on same pace as signaling cascade yet ever-so-specific crowded environment nucleus. However, current understanding how can achieve these feet so quickly efficiently still unclear. In this review, we draw parallels with other protein share our speculations nucleus uses high specificity fidelity. We discuss various constituents TF-condensates, their properties, known unknown functions particular focus steroid signaling-induced programs.

Язык: Английский

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Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation

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

Опубликована: Март 22, 2024

Abstract RNA-binding proteins are central for many biological processes and their characterization has demonstrated a broad range of functions as well wide spectrum target structures. RNA G-quadruplexes important regulatory elements occurring in both coding non-coding transcripts, yet our knowledge structure-based interactions is at present limited. Here, using theoretical predictions experimental approaches, we show that chromatin-binding bind to G-quadruplexes, classify them based on G-quadruplex-binding potential. Combining identification nuclear with computational build prediction tool assigns probability score protein G-quadruplexes. We predicted G-quadruplex exhibit high degree disorder hydrophilicity suggest involvement transcription phase-separation into membrane-less organelles. Finally, the G4-Folded/UNfolded Nuclear Interaction Explorer System (G4-FUNNIES) estimating G4-binding propensities http://service.tartaglialab.com/new_submission/G4FUNNIES .

Язык: Английский

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