Article
Microbiology
Siqi Wang, Leyang Xiang, Fang li, Wenlin Deng, Pinjing Lv, Ye Chen
Summary: This study found that levels of fecal short-chain fatty acids (SCFAs), particularly butyrate, are reduced, and normal colon structure is damaged in patients with CDI compared with those in healthy individuals. Bile acid (BA) metabolic disorder in patients with CDI is characterized by increased primary BA levels and decreased secondary BAs. Butyrate treatment may serve as a novel therapeutic approach for patients with CDI.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Miad Elahi, Haruyuki Nakayama-Imaohji, Masahito Hashimoto, Ayano Tada, Hisashi Yamasaki, Tamiko Nagao, Tomomi Kuwahara
Summary: The gut symbiont Bacteroides thetaiotaomicron (BT) suppresses Clostridium difficile (CD) toxin production by inhibiting polysaccharide metabolism pathways. Polysaccharide fractions derived from BT can suppress CD toxin production, with cell wall-associated glycans playing a key role in this inhibitory effect.
Article
Food Science & Technology
Maria Braune-Yan, Jinfang Jia, Mary Wahba, Johannes Schmid, Panagiotis Papatheodorou, Holger Barth, Katharina Ernst
Summary: Clostridioides difficile infections cause severe symptoms through the secretion of toxins TcdA and TcdB. The drugs VER-155008 and domperidone were found to inhibit TcdB's toxic effects, reduce the glucosylation of Rac1, and protect cells from TcdB-induced damage.
Article
Neurosciences
Runwen Chen, Qiyue Zhang, Yuxing Yan, Yuying Zhang, Tao Zhang
Summary: The study demonstrated that legumain-KO effectively attenuated cognitive impairments, improved synaptic plasticity, and inhibited neuroinflammation in A beta(1-42)-treated mice. Additionally, legumain-KO reduced neuroinflammation by inhibiting the TLR4/MyD88/NF-kappa B pathway, suggesting a potential therapeutic target for Alzheimer's disease.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kimberly A. Harris, Nicole B. Odzer, Ronald R. Breaker
MOLECULAR MICROBIOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Madeline E. Sherlock, Ronald R. Breaker
Article
Biochemistry & Molecular Biology
Diane Yu, Ronald R. Breaker
Article
Biochemistry & Molecular Biology
Ronald R. Breaker
ACS CHEMICAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Sarah N. Malkowski, Ruben M. Atilho, Etienne B. Greenlee, Christina E. Weinberg, Ronald R. Breaker
Article
Biochemistry & Molecular Biology
Shanker S. S. Panchapakesan, Lukas Corey, Sarah N. Malkowski, Gadareth Higgs, Ronald R. Breaker
Summary: A bacterial noncoding RNA motif associated with pnuC genes may function as aptamers for a novel class of NAD(+)-sensing riboswitches, selectively binding NAD(+), nicotinamide mononucleotide (NMN), and NR. These findings suggest that pnuC motif RNAs could be members of a second riboswitch class that regulates gene expression in response to NAD(+) binding.
Article
Biochemistry & Molecular Biology
Hubert Salvail, Aparaajita Balaji, Diane Yu, Adam Roth, Ronald R. Breaker
Article
Biochemistry & Molecular Biology
Shanker S. S. Panchapakesan, Ronald R. Breaker
Summary: The RNA World theory suggests that sophisticated ribozymes and riboswitches played a key role in metabolic processes in ancient organisms, and various types of catalytic RNAs and ligand-sensing RNA switches still exist in modern cells. However, the fusion of RNA enzyme and RNA switch components to form allosteric ribozymes is rare in today's biological systems, despite the abundance of self-cleaving ribozymes and riboswitch aptamers.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kenneth Brewer, Etienne B. Greenlee, Gadareth Higgs, Diane Yu, Gayan Mirihana Arachchilage, Xi Chen, Nicholas King, Neil White, Ronald R. Breaker
Summary: Comparative sequence analysis methods are highly effective in uncovering novel classes of structured noncoding RNAs from bacterial genomic DNA sequences. A computational pipeline was developed to comprehensively identify structured ncRNA representatives from individual bacterial genomes. The findings support the prediction that hundreds of new riboswitch classes and other ncRNAs remain undiscovered among a limited number of completely sequenced bacterial species.
Article
Biology
Xavier Portillo, Yu-Ting Huang, Ronald R. Breaker, David P. Horning, Gerald F. Joyce
Summary: A study has shown that through evolution, an RNA polymerase ribozyme underwent significant structural changes to develop a new tertiary structural element that improved catalytic activity. The evolving population stabilized the new structure, leading to the discovery of a new fitness locale and the potential for further enhancement of polymerase activity.
Article
Biochemistry & Molecular Biology
Ronald R. Breaker
Summary: More than 55 types of riboswitches that respond to small metabolites or elemental ions have been experimentally proven. These riboswitches primarily sense ligands that are fundamental and likely to have been relevant to ancient life forms, including the RNA World. This article discusses the ligands sensed by common riboswitches in modern bacteria and their implications for ancient biological processes. Despite representing most major aspects of metabolism, there are sensory gaps in key areas, which could reveal weaknesses in RNA's performance during RNA World evolution or identify opportunities for discovering new riboswitch classes.
Article
Biochemistry & Molecular Biology
Neil White, Harini Sadeeshkumar, Anna Sun, Narasimhan Sudarsan, Ronald R. Breaker
Summary: Organisms have mechanisms to monitor and adapt to changes in cellular Na+ concentrations. A riboswitch class called "DUF1646 motif" has been discovered to selectively sense Na+ and regulate gene expression relevant to sodium biology. These findings reveal that some bacteria use Na+ riboswitches to monitor, adjust, and exploit Na+ concentrations and gradients.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kumari Kavita, Ronald R. Breaker
Summary: Riboswitches are structured noncoding RNA domains used by bacteria to monitor target ligand concentrations and regulate gene expression. Over 55 distinct classes of natural riboswitches have been discovered in the past 20 years, with potential existence of thousands more. Some riboswitches might have evolved from ancient RNA-based sensors and switches before the emergence of proteins. This article provides an overview of riboswitch research, focusing on their discovery and discussing the challenges faced by researchers in the field.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michael G. Mohsen, Matthew K. Midy, Aparaajita Balaji, Ronald R. Breaker
Summary: Researchers have discovered that some engineered aptamers that work well in test tubes may fail to function in cells. To address this issue, they developed the 'Graftamer' approach, using the architecture of a natural riboswitch to improve aptamer selection in vitro and accelerate testing in vivo. The researchers successfully obtained aptamers for quinine, guanine, and caffeine through multiplexed in vitro selection, and these aptamers maintained the structural features of the natural guanine riboswitch aptamer. By grafting the quinine and caffeine aptamers onto a natural guanine riboswitch expression platform, they confirmed their function in cells. They also identified a class of RNA sequences that evaded the selection strategy and gained insight for future improvements.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Ronald R. Breaker, Kimberly A. Harris, Seth E. Lyon, Freya D. R. Wencker, Chrishan M. Fernando
Summary: OLE RNA is a 600-nucleotide noncoding RNA found in Gram-positive bacteria that thrive in extreme environments. Its precise biochemical functions are unknown, but it forms a ribonucleoprotein (RNP) complex localized to cell membranes. Genetic disruption of OLE RNA causes reduced cell growth under stress conditions, suggesting its involvement in cellular processes and adaptations. We propose that OLE RNP complex is functionally equivalent to eukaryotic TOR complexes in coordinating cell growth and survival.
MOLECULAR MICROBIOLOGY
(2023)