A Compendium of G-flipon Biological Functions that have Experimental Validation

Опубликована: Авг. 23, 2024

As with all new fields of discovery, work on the biological role G-quadruplexes (GQ) has produced a number results that at first glance are quite baffling, sometimes because they do not fit well together, but mostly different from commonly held expectations. Like other classes flipons, those form have repeat sequence motif enables fold. The canonical DNA (G3N1-7)3G3, where N is any nucleotide and G guanine, feature under active selection in avian mammalian genomes. involvement G-flipons genome maintenance traces back to invertebrate C. elegans ancient repair pathways. A for GQ transcription supported by observation yeast Rap1 protein binds both B-DNA, sequence-specific manner, GQ, structure-specific through same helix. Other factors (TF) also engage conformations. RNAs can modulate formation manner cellular machinery as localized TF, linking RNA world modern world. coevolution proteins studies early embryonic development, transient potentially coordinates epigenetic specification cell fate.

Язык: Английский

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Benchmarking DNA large language models on quadruplexes

Computational and Structural Biotechnology Journal, Год журнала: 2025, Номер 27, С. 992 - 1000

Опубликована: Янв. 1, 2025

Large language models (LLMs) in genomics have successfully predicted various functional genomic elements. While their performance is typically evaluated using benchmark datasets, it remains unclear which LLM best suited for specific downstream tasks, particularly generating whole-genome annotations. Current LLMs fall into three main categories: transformer-based models, long convolution-based and state-space (SSMs). In this study, we benchmarked different types of architectures maps G-quadruplexes (GQ), a type flipons, or non-B DNA structures, characterized by distinctive patterns roles diverse regulatory contexts. Although GQ forms from folding guanosine residues tetrads, the computational task challenging as bases involved may be on strands, separated large number nucleotides, made RNA rather than DNA. All performed comparably well, with DNABERT-2 HyenaDNA achieving superior results based F1 MCC. Analysis annotations revealed that recovered more quadruplexes distal enhancers intronic regions. The were better to detecting arrays likely contribute nuclear condensates gene transcription chromosomal scaffolds. Caduceus formed separate grouping generated de novo quadruplexes, while clustered together. Overall, our findings suggest complement each other. Genomic varying context lengths can detect distinct elements, underscoring importance selecting appropriate model task. code data underlying article are available at https://github.com/powidla/G4s-FMs.

Язык: Английский

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Zα and Zβ Localize ADAR1 to Flipons That Modulate Innate Immunity, Alternative Splicing, and Nonsynonymous RNA Editing

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2422 - 2422

Опубликована: Март 7, 2025

The double-stranded RNA editing enzyme ADAR1 connects two forms of genetic programming, one based on codons and the other flipons. recodes in pre-mRNA by deaminating adenosine to form inosine, which is translated as guanosine. also plays essential roles immune defense against viruses cancers recognizing left-handed Z-DNA Z-RNA (collectively called ZNA). Here, we review various aspects biology, starting with progressing has major isoforms, p110 protein lacking p150 Zα domain that binds ZNAs high affinity. isoform induced interferon targets ALU inverted repeats, a class endogenous retroelement promotes their transcription retrotransposition incorporating Z-flipons encode G-flipons G-quadruplexes (GQ). Both include Zβ related but does not bind ZNAs. Here report strong evidence GQ are formed co-transcriptionally repeats within R-loops. By binding GQ, suppresses ALU-mediated alternative splicing, generates most reported nonsynonymous edits R-loop resolution. recognition nucleic acid conformations programming flipons encoding information codons. findings suggest into editmers might improve therapeutic efficacy ADAR1.

Язык: Английский

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Data augmentation with generative models improves detection of Non-B DNA structures

Computers in Biology and Medicine, Год журнала: 2024, Номер 184, С. 109440 - 109440

Опубликована: Ноя. 16, 2024

Язык: Английский

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