Center for RNA Biomedicine

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Publication Highlights

Stressed cellular proteins break social distancing rules

By Elisabeth Paymal

A team of scientists associated with the University of Michigan Center for RNA Biomedicine discovered unexpected cellular adaptation mechanisms in response to dehydration. The observed protein reaction has never been reported before.

The research began while observing processing bodies (P-Bodies), which are membrane-less organelles (MLO) involved in RNA degradation in human cells. The team found that, in response to osmotic changes provoked by high saline or sugar concentrations and subsequent dehydration, many proteins within the cell form aggregates similar to P-Bodies. The reaction takes only a few seconds and is reversible.

This phenomenon is distinct from the well-known integrated stress response that leads to the formation of stress granules, another type of membrane-less organelle that aggregates over several minutes.

“At the fundamental level, our work has unraveled a new paradigm for subcellular (membrane-less) organization and rapid stress response,” says Sethu Pitchiaya, a biophysical chemist, one of two shared first authors and a co-senior author on this publication.

Illustration: A pink cell experiences a gradient of salt levels, depicted as crystals. In response to changes in external salt levels, “clouds” of protein form by phase separation. These protect against the dehydrating effects of salt. (Illustration, Elisabeth Paymal) [Read more…] about Stressed cellular proteins break social distancing rules

Transposable elements play an important role in genetic expression and evolution

By Adam Diehl, Alan Boyle, and Elisabeth Paymal, Center for RNA Biomedicine

Until recently, little was known about how transposable elements contribute to gene regulation. These are little pieces of DNA that can replicate themselves and spread out in the genome. Although they make up nearly half of the human genome, these were often ignored and commonly thought of as “useless junk,” with a minimal role, if any at all, in the activity of a cell. A new study by Adam Diehl, Ningxin Ouyang, and Alan Boyle, University of Michigan Medical School and members of the U-M Center for RNA Biomedicine, shows that transposable elements play an important role in regulating genetic expression with implications to advance the understanding of genetic evolution.

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Seeing is believing: The cutting edge of watching single molecules inside human cells

The cell is a complex network of interacting components, or molecules, each of them with its own characteristics and all of them together functioning as a living system. Each of the molecular processes and interactions in the cell bears the risk of becoming dysfunctional, resulting in disease. Biomedical research into processes that power the cell lays the foundation for major therapeutic breakthroughs. However, the minuscule length scales and high speeds at which these intracellular processes take place make it very challenging to observe them directly within a single cell.

Nils Walter’s team at the University of Michigan, Chemistry Department and Center for RNA Biomedicine, has reviewed the latest research on using high-resolution, single molecule fluorescence microscopy tools to study the interactions between molecules in live human cells in real time. The review covers research reported in 85 publications over the last 5 years, aiming to consolidate the developments and disseminate the techniques that can follow multiple molecules at once (“multiplexing”). These techniques are relatively easy to implement, and are becoming increasingly available and affordable.

Red RNA molecules are docking onto green processing bodies containing RNA degrading enzymes.

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Publication in Nature Neuroscience: Disease-causing Repeats Help Human Neurons Function

Photo of before and after treatment

Before and after treatment

Over half of our genomes are made of repeating elements within DNA. In rare cases, these repeats can become unstable and grow in size. These repeat “expansions” cause neurodegenerative diseases such as ALS and Dementia as well as learning disorders and autism in Fragile X syndrome. Research to date has focused on how these expanded repeats cause disease, but little attention has been given to the repeats themselves and whether they might have normal functions in genes.

By focusing on the biology of healthy nerve cells, a team from the University of Michigan Department of Neurology found that repeats in the gene that causes Fragile X Syndrome normally regulate how and when proteins are made in neurons. This process may be important for learning and memory in these nerve cells and potentially in people. “The repeats function like a switch, slowing down protein production and then quickly turning things back on,” explains Peter Todd, MD., Ph.D., and Principal Investigator of this research.

[Read more…] about Publication in Nature Neuroscience: Disease-causing Repeats Help Human Neurons Function