The RNA of Escherichia coli infected with RNA bacteriophage Q beta was isolated and screened for replicable short-chained RNA. In contrast to earlier assumptions we show that (i) short-chained replicable RNA is a very minor part of the RNA synthesized in the infection cycle, and (ii) that the replicable RNA isolated from infected cells is derived from cellular RNA, in particular 23 S rRNA and 10 Sa RNA, and from Q beta RNA itself. None of the many RNA species known from in vitro experiments was found. The RNA species isolated were all inefficient templates. No replicable RNA could be isolated from non-infected cells. Even in cells expressing high amounts of Q beta replicase very few RNA species could be isolated. RNA generated in vitro in template-free synthesis is therefore not derived from RNA species found in vivo, and replicable RNA found in vitro is generated by a mechanism fundamentally different from the one operating in vivo.
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http://dx.doi.org/10.1006/jmbi.1997.1496 | DOI Listing |
J Med Chem
January 2025
Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.
View Article and Find Full Text PDFACS Nano
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Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
A major challenge in the field of synthetic motors relates to mimicking the precise, motion of biological motor proteins, which mediates processes such as cargo transport, cell locomotion, and cell division. To address this challenge, we developed a system to control the motion of DNA-based synthetic motors using light. DNA motors are composed of a central chassis particle modified with DNA "legs" that hybridize to RNA "fuel", and move upon enzymatic consumption of RNA.
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Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
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Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
The ionizable lipid component of lipid nanoparticle (LNP) formulations is essential for mRNA delivery by facilitating endosomal escape. Conventionally, these lipids are synthesized through complex, multistep chemical processes that are both time-consuming and require significant engineering. Furthermore, the development of new ionizable lipids is hindered by a limited understanding of the structure-activity relationships essential for effective mRNA delivery.
View Article and Find Full Text PDFCirc Res
January 2025
Department of Integrative Physiology (W.G.P., J.F.M.), Baylor College of Medicine, Houston, TX.
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