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Riboswitches are cis-acting elements that regulate gene expression by affecting transcriptional termination or translational initiation in response to binding of a metabolite. A typical riboswitch is made of an upstream aptamer domain and a downstream expression platform. Both domains participate in the folding and structural rearrangement in the absence or presence of its cognate metabolite. RNA polymerase pausing is a fundamental property of transcription that can influence RNA folding. Here we show that pausing plays an important role in the folding and conformational rearrangement of the Escherichia coli btuB riboswitch during transcription by the E. coli RNA polymerase. This riboswitch consists of an approximately 200 nucleotide, coenzyme B12 binding aptamer domain and an approximately 40 nucleotide expression platform that controls the ribosome access for translational initiation. We found that transcriptional pauses at strategic locations facilitate folding and structural rearrangement of the full-length riboswitch, but have minimal effect on the folding of the isolated aptamer domain. Pausing at these regulatory sites blocks the formation of alternate structures and plays a chaperoning role that couples folding of the aptamer domain and the expression platform. Pausing at strategic locations may be a general mechanism for coordinated folding and conformational rearrangements of riboswitch structures that underlie their response to environmental cues.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295289 | PMC |
http://dx.doi.org/10.1073/pnas.1113086109 | DOI Listing |
Int J Biol Macromol
December 2024
School of Health Science and Engineering, Shanghai Engineering Research Center of Food Rapid Detection, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address:
Aptamer conformations are susceptible to environmental conditions, which makes it difficult to achieve stable targets detection in complex environments with aptasensors. Imprinting strategy was proposed to immobilize the specific conformation of aptamers, aiming to enhance their recognition anti-interference. However, it is mechanistically unclear how the imprinted polymers affect aptamers' recognition, which limits application of the strategy.
View Article and Find Full Text PDFAnal Chem
December 2024
School of Food Science and Technology, Jiangnan University, Wuxi 214122, People's Republic of China.
The recognition of small molecules plays a crucial role in disease diagnosis, environmental assessment, and food safety. Currently, their recognition elements predominantly rely on antibodies and aptamers while suffering from a limitation of the complex screening process due to the low immunogenicity of small molecules. Herein, we present a top-down computational design strategy for molecule recognition peptides (MRPs) for enzyme-peptide self-assembly and chemiluminescence biosensing.
View Article and Find Full Text PDFSmall Methods
December 2024
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
Multimeric aptamer strategies are often adopted to improve the binding affinity of an aptamer toward its target molecules. In most cases, multimeric aptamers are constructed by connecting pre-identified monomeric aptamers derived from in vitro selection. Although multimerization provides an added benefit of enhanced binding avidity, the characterization of different aptamer pairings adds more steps to an already lengthy procedure.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2024
State Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Breast cancer with positive expression of estrogen receptor α (ERα+) accounts for 70% of breast cancer cases, whose predominant treatment is currently endocrine therapy. The main strategy of endocrine therapy for ERα+ breast cancer is to inhibit the ERα signaling pathway and downregulate ERα levels, which often results in mutations in the ligand-binding domain (LBD) of ERα, leading to significant resistance to subsequent treatment in patients. To combat drug resistance, we first proposed a novel aptamer PROTAC strategy through specifically targeted degradation of ERα via targeting the DNA-binding domain (DBD) of ERα.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Tűzoltó street 37-47., 1094 Budapest, Hungary. Electronic address:
Streptococcus mutans is a commensal oral bacterium, yet its capacity for extensive biofilm formation is a major contributor to dental caries. This study presents a novel biofilm inhibition strategy by targeting GbpC, a cornerstone protein in S. mutans biofilm architecture, with specific DNA aptamers.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!