Discovery of two novel classes of natural products with activity against RNA viruses

Zwei neue Naturstoffklassen mit Wirksamkeit gegen RNA-Viren entdeckt

New function of a known defence mechanism discovered: RNA interference not only fights viruses, it also regulates the protein balance of intestinal cells / Publication in ‘Nature Cell Biology’

Neue Funktion eines bekannten Abwehrmechanismus entdeckt: Die RNA Interferenz bekämpft nicht nur Viren, sie reguliert auch das Proteingleichgewicht der Darmzellen / Veröffentlichung in „Nature Cell Biology“

Basic researchers at Leipzig University have solved a puzzle in the evolution of bacterial enzymes. By reconstructing a candidate for a special RNA polymerase as it existed about two billion years ago, they were able to explain a hitherto puzzling property of the corresponding modern enzymes. Unlike their ancestors, they do not work continuously and are thus significantly more effective – these pauses in activity constitute evolutionary progress. The reconstruction of the protein from prehistoric times was made possible thanks to interdisciplinary cooperation between molecular biochemistry and bioinformatics.

If introns remain in certain RNAs, worms live longer

The control of RNA metabolism is crucial to the regulation of animal longevity, researchers from the Max Planck Institute for Biology of Ageing in Cologne have now discovered. They found that worms live longer when certain RNAs are processed differently during RNA maturation. This could be an additional way for organisms to control the ageing process.

Mitochondrien, die Kraftwerke der Zelle, enthalten eigenes Erbgut und eigene RNA-Moleküle. Ein Team vom Deutschen Krebsforschungszentrum fanden nun heraus: Bestimmte Markierungen der mitochondrialen RNA begünstigen die invasive Ausbreitung von Krebszellen. Genetische Marker für eine starke mitochondriale RNA-Markierung sind bei Patienten mit Kopf-Hals-Tumoren mit metastasierender Erkrankung verbunden.
Blockierten die Forscher in Krebszellen das für die RNA-Markierungen verantwortliche Enzym, so reduzierte dies die Anzahl der Metastasen. Auch Antibiotika, die die Proteinsynthese in den Mitochondrien unterdrücken, konnten die invasive Ausbreitung von Krebszellen im Laborversuch verhindern.

Fast alle Zelltypen sondern Exosomen ab: kleine extrazelluläre Vesikel, die mit Proteinen, RNA und DNA beladen sind. Auf diese Weise können Zellen untereinander kommunizieren und stimmen viele Prozesse ab, wie beispielsweise Zellteilungen. In der Nähe von Tumoren werden solche Exosomen verstärkt abgesondert. „Die darin enthaltenen Biomoleküle verändern die Umgebung von Tumoren und können damit den Verlauf einer Krebserkrankung entscheidend beeinflussen“, so PD Dr. Basant Kumar Thakur von der Kinderklinik III des Universitätsklinikums Essen und Wissenschaftler der Medizinischen Fakultät der Universität Duisburg-Essen.

HIRI scientists show that target RNA levels influence defense against invaders

A new protein subunit vaccine may offer an inexpensive, easy-to-store, and effective alternative to RNA vaccines for COVID-19.

A new study shows how certain RNA molecules control the repair of damaged DNA in cancer cells, a discovery that could eventually give rise to better cancer treatments.

Living organisms produce an abundance of small molecular compounds, called metabolites. Although, it is clear that small molecules are central to all aspect of life, their exact functionalities are often unknown. To fill this knowledge gap, and because small molecules act by binding with proteins, Aleksandra Skirycz’s group at the Max Planck Institute of Molecular Plant Physiology developed a novel strategy to identify such protein-molecule complexes. An important group of small molecules identified by this novel strategy are 2′,3′-cAMP nucleotides, which are products of RNA degradation and appear to play an important role in the regulation of stress responses.

In the long-term battle between a herpesvirus and its human host, a virologist and her team of students have identified some human RNA able to resist the viral takeover — and the mechanism by which that occurs.

During infection, the yeast Candida albicans stimulates the release of tiny RNA fragments, which then stimulate its own growth. An international research team led by the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena has discovered this unusual exploitation of the human immune system. The findings can explain disease processes and provide new approaches for the therapy of fungal infections. The results were published in the journal mBio.

Scientists believe it may be possible to prevent DNA changes driven by two proteins highly active in leukemia and other cancers. They recently reported a new mechanistic target for drug development.

A genome study to look for variants in a gene considered a fundamental building block for microscopic structures that synthesize proteins took a surprising twist.

RNA has already been making an impact in the context of the vaccine program, but the potential of RNA-based compounds is far from being fully tapped, as RNA allows for entirely new therapeutic approaches. Prof. Thomas Thum, Co-Institute Director of the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, has developed a form of RNA therapy for treating heart failure, which has already been successfully tested in patients as part of a phase 1b clinical trial. Other RNA therapies are currently being developed to treat pulmonary fibrosis and other forms of organ fibrosis.

Dresden scientists find that lipids modulate RNA activity, a possible clue to origin of life and tool for synthetic biology.

EMBARGO: DO NOT PUBLISH BEFORE 12/22/2021, 5:00 PM.

Physical biology: Publication in Nature

DNAzymes are precision biocatalysts that destroy unwanted RNA molecules. However, major obstacles to their use in medicine remain. Together with Jülich Research Centre (FZJ) and the University of Bonn, a research team from Heinrich Heine University Düsseldorf (HHU) has investigated with atomic resolution how DNAzymes work in real time. They have now presented these important fundamental findings and their application in the renowned journal “Nature”.

Researchers have discovered a nanoparticle released from cells, called a ’supermere,‘ which contains enzymes, proteins and RNA associated with multiple cancers, cardiovascular disease, Alzheimer’s disease and even COVID-19.

A new study has identified an RNA molecule that suppresses prostate tumors. The scientists found that prostate cancers develop ways to shut down this RNA molecule to allow themselves to grow. According to the new research — conducted in mice implanted with human prostate tumor samples — restoring this so-called long noncoding RNA could be a new strategy to treat prostate cancer that has developed resistance to hormonal therapies.

Researchers have designed a way to selectively turn on gene expression in target cells, including human cells. Their technology can detect specific mRNA sequences, which triggers production of a specific protein.

Die RNA hat viele wichtige Funktionen in unserem Körper und wird seit kurzem auch als Corona-Impfstoff genutzt. Doch das Lebensmolekül ist längst noch nicht lückenlos durchschaut. Sind zuckerhaltige RNA-Moleküle als Signalstoffe für das Immunsystem unterwegs?

Researchers have shown for the first time how mutations affecting a cellular process called RNA splicing alter cells to develop myelodysplastic syndrome (MDS) and other hematologic malignancies and solid tumors.

Researchers identified a small RNA molecule called miR-766-5p that reduces expression of MYC, a critical cancer-promoting gene. This microRNA reduces levels of proteins CBP and BRD4, which are both involved in super-enhancer (SE) formation. SEs form in areas of DNA that can fuel MYC expression and tumor progression. This study provides strong evidence for developing miR-766-5p as a novel therapeutic to treat MYC-driven cancers.