Circular L-RNA aptamer promotes target recognition and controls gene activity DOI Creative Commons
Danyang Ji, Kaixin Lyu, Haizhou Zhao

и другие.

Nucleic Acids Research, Год журнала: 2021, Номер 49(13), С. 7280 - 7291

Опубликована: Июнь 28, 2021

Abstract Rational design of aptamers to incorporate unnatural nucleotides and special chemical moieties can expand their functional complexity diversity. Spiegelmer (L-RNA aptamer) is a unique class aptamer that composed L-RNA nucleotides, so far there are limited candidates applications being reported. Moreover, the target binding properties current require significant improvement. Here, using L-Apt.4-1c as an example, we develop simple robust strategy generate first circular aptamer, cycL-Apt.4-1c, quantitatively, demonstrate substantial enhancement in affinity selectivity toward its target, notably report novel controlling RNA–protein interaction, gene activity including telomerase expression. Our approach findings will be applicable any open up new avenue for diverse applications.

Язык: Английский

Comprehensive analysis of intramolecular G-quadruplex structures: furthering the understanding of their formalism DOI Creative Commons

Marc Farag,

Liliane Mouawad

Nucleic Acids Research, Год журнала: 2024, Номер 52(7), С. 3522 - 3546

Опубликована: Март 21, 2024

Abstract G-quadruplexes (G4) are helical structures found in guanine-rich DNA or RNA sequences. Generally, their formalism is based on a few dozen structures, which can produce some inconsistencies incompleteness. Using the website ASC-G4, we analyzed of 333 intramolecular G4s, all types, allowed us to clarify key concepts and present new information. To each eight distinguishable topologies corresponds groove-width signature predominant glycosidic configuration (gc) pattern governed by directions strands. The relative orientations stacking guanines within strands, quantified related vertical gc successions, determine twist tilt helices. latter impact minimum groove widths, represent space available for lateral ligand binding. G4 four helices have similar twists, even when these twists irregular, meaning that they various angles along Despite its importance, succession has no strict one-to-one relationship with topology, explains discrepancy between corresponding circular dichroism spectra. This study introduce concept platypus properties several topologies.

Язык: Английский

Процитировано

15
RNA G-quadruplexes and stress: emerging mechanisms and functions DOI
Prakash Kharel, Pavel Ivanov

Trends in Cell Biology, Год журнала: 2024, Номер 34(9), С. 771 - 784

Опубликована: Фев. 9, 2024

Язык: Английский

Процитировано

14
G-quadruplex folding in Xist RNA antagonizes PRC2 activity for stepwise regulation of X chromosome inactivation DOI
Yong Woo Lee,

Uri Weissbein,

Roy Blum

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(10), С. 1870 - 1885.e9

Опубликована: Май 1, 2024

Язык: Английский

Процитировано

12
G-Quadruplexes and the DNA/RNA helicase DHX36 in health, disease, and aging DOI Creative Commons
Aaron Antcliff, Louise D. McCullough, Andrey S. Tsvetkov

и другие.

Aging, Год журнала: 2021, Номер 13(23), С. 25578 - 25587

Опубликована: Дек. 4, 2021

G-Quadruplex (G4) DNA (G4 DNA) and RNA RNA) are secondary nucleic acid structures that have multiple roles in vital cellular processes. G4 DNA- RNA-binding proteins unwinding helicases associate with regulate G4s during virtually all processes involve RNA. DEAH-Box helicase 36 (DHX36), a member of the large DExD/H box family, enzymatically unwinds both By exerting its function, DHX36 regulates transcription, genomic stability, telomere maintenance, translation metabolism. This review will provide an overview DHX36, including DHX36’s potential role neuronal development neurodegeneration. We conclude discussion possible functions aging brain.

Язык: Английский

Процитировано

45
Machine Learning Informs RNA‐Binding Chemical Space** DOI
Kamyar Yazdani,

Deondre Jordan,

Mo Yang

и другие.

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(11)

Опубликована: Дек. 30, 2022

Abstract Small molecule targeting of RNA has emerged as a new frontier in medicinal chemistry, but compared to the protein literature our understanding chemical matter that binds is limited. In this study, we reported R epository O f BI nders N ucleic acids (ROBIN), library nucleic acid binders identified by small microarray (SMM) screening. The complete results 36 individual SMM screens against 24 572 molecules were (including total 1 627 072 interactions assayed). A set 2 003 RNA‐binding was identified, representing largest fully public, experimentally derived its kind date. Machine learning used develop highly predictive and interpretable models characterize molecules. This work demonstrates machine algorithms applied sets are powerful method inform RNA‐targeted space.

Язык: Английский

Процитировано

37
Discovering molecular features of intrinsically disordered regions by using evolution for contrastive learning DOI Creative Commons
Alex X. Lu,

Amy X. Lu,

Iva Pritišanac

и другие.

PLoS Computational Biology, Год журнала: 2022, Номер 18(6), С. e1010238 - e1010238

Опубликована: Июнь 29, 2022

A major challenge to the characterization of intrinsically disordered regions (IDRs), which are widespread in proteome, but relatively poorly understood, is identification molecular features that mediate functions these regions, such as short motifs, amino acid repeats and physicochemical properties. Here, we introduce a proteome-scale feature discovery approach for IDRs. Our approach, call "reverse homology", exploits principle important functional conserved over evolution. We use this contrastive learning signal deep learning: given set homologous IDRs, neural network has correctly choose held-out homolog from another IDRs sampled randomly proteome. pair reverse homology with simple architecture standard interpretation techniques, show learns can be interpreted repeats, or bulk like charge propensities. also our model used produce visualizations what residues most IDR function, generating hypotheses uncharacterized results suggest using unsupervised networks promising avenue gain systematic insight into understood protein sequences.

Язык: Английский

Процитировано

35
Cell death or survival: Insights into the role of mRNA translational control DOI Creative Commons
Nupur Bhatter, Sergey E. Dmitriev, Pavel Ivanov

и другие.

Seminars in Cell and Developmental Biology, Год журнала: 2023, Номер 154, С. 138 - 154

Опубликована: Июнь 24, 2023

Язык: Английский

Процитировано

20
HNRNPH1 regulates the neuroprotective cold‐shock protein RBM3 expression through poison exon exclusion DOI Creative Commons
Julie Qiaojin Lin, Deepak Khuperkar,

Sofia Pavlou

и другие.

The EMBO Journal, Год журнала: 2023, Номер 42(14)

Опубликована: Май 30, 2023

Abstract Enhanced expression of the cold‐shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and vivo . Whilst upstream signalling pathways leading to RBM3 have been described, precise molecular mechanism cold induction remains elusive. To identify temperature‐dependent modulators RBM3, we performed a genome‐wide CRISPR‐Cas9 knockout screen using RBM3‐reporter human iPSC‐derived neurons. We found that mRNA levels are robustly regulated by several splicing factors, with heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) being strongest positive regulator. Splicing analysis revealed moderate hypothermia significantly represses inclusion poison exon, which, when retained, targets for nonsense‐mediated decay. Importantly, show HNRNPH1 mediates this cold‐dependent exon skipping via its thermosensitive interaction G‐rich within exon. Our study provides novel mechanistic insights into regulation further therapeutic strategies.

Язык: Английский

Процитировано

16
Cellular Visualization of G-Quadruplex RNA via Fluorescence- Lifetime Imaging Microscopy DOI Creative Commons
Jenna Robinson, Stine G. Stenspil, Karolina Maleckaitė

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 146(1), С. 1009 - 1018

Опубликована: Дек. 27, 2023

Over the past decade, appreciation of roles G-quadruplex (G4) structures in cellular regulation and maintenance has rapidly grown, making establishment robust methods to visualize G4s increasingly important. Fluorescent probes are commonly used for G4 detection vitro; however, achieving sufficient selectivity detect a dense structurally diverse environment is challenging. The use fluorescent further complicated by variations probe uptake into cells, which may affect fluorescence intensity independently abundance. In this work, we report an alternative small-molecule approach that does not rely on switch-on and, thus, require molecules with exclusive binding selectivity. Specifically, have developed novel thiazole orange derivative, TOR-G4, exhibits unique lifetime when bound compared other structures, allowing be sensitively distinguished from non-G4 binding, independent local concentration. Furthermore, TOR-G4 primarily colocalizes RNA cytoplasm nucleoli it first lifetime-based validated exploring emerging cellulo.

Язык: Английский

Процитировано

16
Structural overview of DNA and RNA G-quadruplexes in their interaction with proteins DOI Creative Commons
Romualdo Troisi, Filomena Sica

Current Opinion in Structural Biology, Год журнала: 2024, Номер 87, С. 102846 - 102846

Опубликована: Июнь 7, 2024

Since the discovery of G-quadruplex (G4) participation in vital cellular processes, regulation interaction naturally occurring G4s with relative target proteins has emerged as a promising approach for therapeutic development. Additionally, synthetic strategy produced several oligonucleotide aptamers, embodying G4 module, which exhibit relevant biological activity by binding selectively to protein. In this context, G4-protein structures available Protein Data Bank represent valuable molecular view different topologies involved protein interaction. Interestingly, recent results have shown co-existence other structural domains such duplexes. Overall, these findings allow better understanding mechanisms that regulate intricate functions and suggest new design innovative medical treatments.

Язык: Английский

Процитировано

7