A5089760479- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- RNA Research and Splicing
- Advanced Electron Microscopy Techniques and Applications
- Origins and Evolution of Life
- Cancer-related molecular mechanisms research
- Bacteriophages and microbial interactions
- Semiconductor materials and interfaces
- Circular RNAs in diseases
- Nanowire Synthesis and Applications
- Force Microscopy Techniques and Applications
- Bacterial Genetics and Biotechnology
- Porphyrin and Phthalocyanine Chemistry
- Photodynamic Therapy Research Studies
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- Nanoplatforms for cancer theranostics
- Photosynthetic Processes and Mechanisms
- Advanced NMR Techniques and Applications
Aarhus University
2021-2024
MRC Laboratory of Molecular Biology
2024
Medical Research Council
2024
Houston Methodist
2023-2024
National Clinical Research
2023
State Key Laboratory of Biotherapy
2023
Sichuan University
2023
West China Hospital of Sichuan University
2023
University of Manitoba
2014-2020
Guanine quadruplexes (G4s) are an important structure of nucleic acids (DNA and RNA) with roles in several cellular processes. RNA G4s require specialized unwinding enzymes, which only two have been previously identified. We describe the results a simple specific mass spectrometry guided method used to screen HEK293T cell lysate for G4 binding proteins. From these results, we validated helicase protein DDX21. DDX21 is established helicase, but has not yet as protein. Through biochemical...
Abstract The first RNA category of the Critical Assessment Techniques for Structure Prediction competition was only made possible because scientists who provided experimental structures to challenge predictors. In this article, these offer a unique and valuable analysis both successes areas improvement in predicted models. All 10 RNA‐only targets yielded predictions topologically similar experimentally determined structures. For one target, experimentalists were able phase their x‐ray...
Cryogenic electron microscopy (cryo-EM) is a promising method for characterizing the structure of larger RNA structures and complexes. However, individual aptamers difficult to solve by cryo-EM due their low molecular weight high signal-to-noise ratio. By placing on scaffolds, contrast can be increased allow determination tertiary aptamer. Here we use origami scaffold two fluorescent (Broccoli Pepper) in close proximity show that cognate fluorophores serve as donor acceptor FRET. Next,...
The emergence of an RNA replicase capable self-replication is considered important stage in the origin life. polymerase ribozymes (PR) - including a variant that uses trinucleotide triphosphates (triplets) as substrates have been created by vitro evolution and are closest functional analogues replicase, but structural basis for their function poorly understood. Here we use single-particle cryogenic electron microscopy (cryo-EM) high-throughput mutation analysis to obtain structure triplet...
BC200 is a long non-coding RNA expressed at high levels in the brain and elevated variety of tumour types. has hypothesized role translational regulation; however, to date functional both normal diseased states remains poorly characterized. Detailed expression analyses were performed tumor cell lines, primary non-tumorigenic cultured breast lung cells, panel human tissues by quantitative real-time PCR confirmed northern blot. Subcellular fractionation was assess distribution efficient...
RNA nanotechnology aims to use as a programmable material create self-assembling nanodevices for application in medicine and synthetic biology. The main challenge is develop advanced robotic devices that both sense, compute, actuate obtain enhanced control over molecular processes. Here, we the origami method prototype an device, named "Traptamer," mechanically traps fluorescent aptamer, iSpinach. Traptamer shown sense two key strands, acts Boolean AND gate, reversibly controls fluorescence...
The identification of four-stranded G-quadruplexes (G4s) has highlighted the fact that DNA additional spatial organisations at its disposal other than double-stranded helices. Recently, it became clear formation G4s is not limited to traditional G3+NL1G3+NL2G3+NL3G3+ sequence motif. Instead, G3 triplets can be interrupted by deoxythymidylate (DNA) or uridylate (RNA) where base forms a bulge loops out from G-quadruplex core. Here, we report first high-resolution X-ray structure unique...
DDX21 is a newly discovered RNA G-quadruplex (rG4) binding protein with no known biological rG4 targets. In this study we used label-free proteomic MS/MS to identify 26 proteins that are expressed at significantly different levels in cells expressing an rG4-binding deficient (M4). MS data available via ProteomeXchange identifier PXD013501. From list validate MAGED2 as regulated by through its 5′-UTR. levels, but not mRNA reduced half M4. has repressive effect on TRAIL-R2 expression relieved...
Nucleic acids rich in guanine are able to fold into unique structures known as G-quadruplexes. G-quadruplexes consist of four tracts guanylates arranged parallel or antiparallel strands that aligned stacked G-quartet planes. The structure is further stabilized by Hoogsteen hydrogen bonds and monovalent cations centered between the RHAU (RNA helicase associated with AU-rich element) a member ATP-dependent DExH/D family RNA helicases can bind resolve contains core domain an N-terminal...
BC200 is a long non-coding RNA primarily expressed in brain but aberrantly various cancers. To gain further understanding of the function BC200, we performed proteomic analyses ribonucleoprotein (RNP) by transfection 3′ DIG-labelled BC200. Protein binding partners functionally related murine BC1 as well scrambled were also assessed both human and mouse cell lines. Stringent validation proteins identified mass spectrometry confirmed 14 84 protein excluded eight that did not appreciably bind...
Abstract RNA nanotechnology takes advantage of structural modularity to build self‐assembling nano‐architectures with applications in medicine and synthetic biology. The use paranemic motifs, that form without unfolding existing secondary structure, allows for the creation nanostructures are compatible cotranscriptional folding vitro vivo. In previous work, kissing‐loop (KL) motifs have been widely used design fold cotranscriptionally. However, crossover (PX) motif has not yet explored...
Abstract The folding of RNA and protein molecules during their synthesis is a crucial self-assembly process that nature employs to convert genetic information into the complex molecular machinery supports life. Misfolding events are cause several diseases, pathway central biomolecules, such as ribosome, strictly regulated by programmed maturation processes chaperones. However, dynamic challenging study because current structure determination methods heavily rely on averaging, existing...
Abstract The RNA world hypothesis is supported by the discovery of polymerase ribozymes that can perform RNA-catalyzed replication processes on different templates. Recently, rolling circle synthesis (RCS) small circular (scRNA) templates has been demonstrated. However, structural and dynamic properties scRNA its products intermediates have never explored. Here we used cryogenic electron microscopy (cryo-EM) to characterize relevant for RCS find these form an unexpectedly diverse group...
Large-scale and continuous conformational changes in the RNA self-folding process present significant challenges for structural studies, often requiring trade-offs between resolution observational scope. Here, we utilize individual-particle cryo-electron tomography (IPET) to examine post-transcriptional of designed origami 6-helix bundle with a clasp helix (6HBC). By avoiding selection, classification, averaging, or chemical fixation optimizing cryo-ET data acquisition parameters,...
ABSTRACT RNA nanotechnology uses motifs from nature as well aptamers in vitro selection to construct nanostructures and devices for applications medicine synthetic biology. The origami method allows cotranscriptional folding of large scaffolds that can position functional a precise manner, which has been verified by Förster Resonance Energy Transfer (FRET) between fluorescent aptamers. Cryogenic electron microscopy (cryo-EM) is promising characterizing the structure larger nanostructures....
Abstract The emergence of an RNA molecule capable replicating itself and other sequences is a central pillar hypotheses regarding the origin life. In vitro evolution has yielded polymerase ribozymes (PR) that can copy range templates using nucleotide or trinucleotide triphosphates (triplets) as substrates may give rise to replicase activity. However, our understanding PR function encumbered by lack structural information beyond progenitor class I ligase (cIL) ribozyme. Here, we report...