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A novel and sensitive trefoil-structured biosensor based on nanoporous gold for simultaneous determination of microRNA-21 and microRNA-16.
Biosens Bioelectron
December 2024
State Key Laboratory of Quality Research in Chinese Medicines & School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China. Electronic address:
Although electrochemical biosensors have been developed to detect multiple microRNAs (miRNAs) simultaneously through loading different capture probes, high surface-induced perturbation and competition among probes have reduced the detection sensitivity. To address these challenges, a trefoil DNA capture probe (TDCP) was designed for microRNA-21 (miR-21) and microRNA-16 (miR-16) detection simultaneously. The TDCP exhibits a stable structure, low spatial resistance, and integral rigidity, which decreases high surface-induced perturbations and competition to improve the accessibility of the target miRNA.
View Article and Find Full Text PDFOrthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array.
Nat Commun
December 2024
Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA.
Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation.
View Article and Find Full Text PDFFunctional and molecular insights into the role of Sae2 C-terminus in the activation of MRX endonuclease.
Nucleic Acids Res
December 2024
Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano - Bicocca, 20126 Milano, Italy.
The yeast Sae2 protein, known as CtIP in mammals, once phosphorylated at Ser267, stimulates the endonuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex to cleave DNA ends that possess hairpin structures or protein blocks, such as the Spo11 transesterase or trapped topoisomerases. Stimulation of the Mre11 endonuclease by Sae2 depends on a Rad50-Sae2 interaction, but the mechanism by which this is achieved remains to be elucidated. Through genetic studies, we show that the absence of the last 23 amino acids from the Sae2 C-terminus specifically impairs MRX-dependent DNA cleavage events, while preserving the other Sae2 functions.
View Article and Find Full Text PDFStructure-function analysis of tRNA tA-catalysis, assembly, and thermostability of Aquifex aeolicus TsaDB tetramer in complex with TsaE.
J Biol Chem
December 2024
School of Life Sciences, Key Laboratory of Cell Activities and Stress Adaptation of the Ministry of Education, Lanzhou University, Lanzhou, China. Electronic address:
Article Synopsis
- The modification of tRNA at position 37 (tA) is crucial for ensuring accurate protein synthesis and is produced through the actions of specific enzymes (TsaC, TsaD, TsaB, and TsaE) using L-threonine and ATP in bacteria.
- This study reconstituted the biosynthesis of tA from the bacterium Aquifex aeolicus and examined the structural characteristics of the TsaDB enzyme complex, finding that it can bind both TsaE and tRNA, with the binding being influenced by specific protein sequences.
- The research showed that TsaE enhances the catalytic action of TsaDB, leading to the release of tRNA
Structure-aware annotation of leucine-rich repeat domains.
PLoS Comput Biol
November 2024
Center for Computational Biology, University of California Berkeley, Berkeley, California, United States of America.
Protein domain annotation is typically done by predictive models such as HMMs trained on sequence motifs. However, sequence-based annotation methods are prone to error, particularly in calling domain boundaries and motifs within them. These methods are limited by a lack of structural information accessible to the model.
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