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Figure 1: Three different non-genetically encoded scaffolds regulate cellular responses. The interactions between them are normally kept in check to ensure that cells remain healthy and functional, with arrows indicating positive interactions and dotted lines with a bar at one end representing inhibitory events. The Z-RNAs expressed from the genome will cause inflammatory cell death when interferon induces high levels of ZBP1 (as indicated by the scarlet shading). That response eliminates virally infected cells, other aged cells that no longer function normally, and those inflamed cells that support the growth of malignancies.

Cellular scaffolding: Crowdsourcing cellular responses in health and disease

In this article, Dr Alan Herbert discusses how different types of cellular scaffolds interact and impact the risk of diseases, citing the example of Z-RNAs pushing cells to inflammatory states in tumors and autoimmune conditions, setting the stage for new therapeutics.

Flipons: The discovery of Z-DNA and soft-wired genomes

Alan Herbert, Founder and President of InsideOutBio, discusses alternative DNA conformations and understanding of their biological functions.
Figure 1. Chemical evolution of type I and type II tRNAs. 3 31 nucleotide minihelices of known sequence were linked to form the 93 nucleotide tRNA precursor, which was processed to type I and type II tRNAs by internal 9 nucleotide deletion(s). The colors are consistent with the model. Molecular graphics were done using ChimeraX

Transfer RNA as a written molecular history of the life transition on earth

Zachary Burton, Ph.D., Professor Emeritus, Department of Biochemistry and Molecular Biology, Michigan State University, reports on tRNA (transfer RNA) as a written molecular history of the pre-life to life transition on Earth ~4 billion years ago.
Alternative flipon conformations compared to Watson and Crick DNA are displayed in the left panel. Flipons offer a new way to program the genome

RNA and DNA flipons in health and disease

Flipons are the next step in DNA research. What they are, their role in DNA and RNA coding, their impact on medical science, and their relation to the immune system are discussed here.
Figure 1. Elements of the operational RNA code in the tRNA acceptor stem. A. Bases in the tRNA acceptor stem encode two aspects of amino acid physical chemistry—size and polarity—that determine protein folding. B. Acceptor stem bases preceded the anticodon stem-loop and code other properties. C. The oldest parts of Class I and II AARS could already discriminate between both amino acid and RNA substrates (6) .

tRNA: The operational RNA code and protein folding

Charles W. Carter, Jr., from the Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, relates molecular recognition used in genetic coding to structures of aminoacyl-tRNA synthetases and their cognate tRNAs.
DNA sequencing gel run science and data genomic genetic analysis background abstract pattern.

Understanding thermolabile protecting groups for nucleic acid-based drugs

Serge L. Beaucage investigates thermolabile protecting groups for the amine functions of purine and pyrimidine deoxyribonucleosides for the development and implementation of synthetic DNA sequences as nucleic acid-based drugs.
Long structure of the DNA double helix in depth of view.

What are the possibilities of DNA and RNA sequences?

Serge L. Beaucage, Supervisory Research Chemist at the Food and Drug Administration discusses his work with DNA and RNA sequences and the groundbreaking impact this technique could have.

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