#microrna

The Nobel Prize in medicine was awarded Monday to Americans Victor Ambros and Gary Ruvkun for their discovery of microRNA, a fundamental principle governing how gene activity is regulated. The Nobel Assembly said that their discovery is "proving to be fundamentally important for how organisms develop and function."

Microdosing

Many diseases wreak havoc not by introducing new villainous elements, like during infections, but by causing harmful changes to innate processes of the body. This is true of chronic obstructive pulmonary disease (COPD), a progressively debilitating condition often caused by smoking. Treatments are limited, so researchers are investigating the mechanisms behind the symptoms. They focussed on microRNAs – tiny strands of genetic material that regulate the expression of particular genes – in patients and in mice exposed to cigarette smoke. They found that the amounts of one particular microRNA, miR-21, increased in the airway linings during COPD progression (pictured, miR-21 in red and lung cells from a COPD patient in blue). Blocking this microRNA reduced inflammation and improved lung function in mice, restoring cellular pathways back to their usual rhythm. By providing a potential target for new treatments, this discovery could be a breath of fresh air for patients.

Written by Anthony Lewis

Image from the cover of Science TM, from work by Richard Y. Kim, Krishna P. Sunkara, Ken R. Bracke & Andrew G. Jarnicki et al

Centre for Inflammation, Centenary Institute and University of Technology Sydney, NSW, Australia

Image copyright held by and reproduced with permission from the AAAS

Research published in Science Translational Medicine, November 2021

Extracellular vesicles: the missing link between NAFLD and atherosclerosis?

Extracellular vesicles containing microRNA-1 are released by the steatotic liver in this depiction of the novel mechanism proposed to link NAFLD with atherosclerosis. Read article here.

Humans have the salamander-like ability to regenerate cartilage in joints. Thoughts heath innovators?

It is known that some animals, such as zebrafish, bichir, and axolotl, with a high regenerative capacity, regulate limb regeneration by a circuit of microRNA. Unlike these animals, humans cannot regenerate whole limbs and are also believed to be unable to counteract the breakdown or damage of cartilage and the development of osteoarthritis. Now, a study from Duke University shows cartilage in…

Micro Expression

Gene expression involves two key stages: transcribing a section of DNA into an mRNA molecule, then translating that into a protein. The process is modulated by sophisticated regulatory systems, including microRNAs (or miRNAs), small segments of RNA that bind to mRNAs to inactivate them. miRNAs are known to be crucial for development, but identifying their specific roles is complicated. In the spinal cord, distinct types of neurons (shown in different colours in this cross-section from a mouse) are distinguished by the genes they express, and miRNAs are involved in this differentiation. In mice, recent research found that the loss of six miRNAs, the Mi34/449 group, alters the pattern of gene expression in spinal cord neurons, affecting their neural circuits. Mice lacking Mi34/449 also have external symptoms, such as unusual posture and greater heat sensitivity, providing an example of how miRNAs can help define cell populations, with far-reaching consequences for behaviour.

Written by Emmanuelle Briolat

Image from work by Shih-Hsin Chang and colleagues

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, March 2021

Micro Diet

After a year’s various indulgences, some of us will make resolutions to exercise more. This not only burns off calories, but also fuels the body’s capacity to keep weight under control, in part by boosting microRNAs – small strands of genetic material that can promote energy use. An alternative way to trigger this process might help people accomplish their weight-loss goals. A new study has looked at how enoxacin – an antibiotic rarely used any more – can encourage metabolism in cells and hence keep weight down. In experiments with mice, it caused microRNAs to make obesity-promoting white fat (which stores surplus energy as fat) behave like brown fat (which turns food to heat), and increased energy expenditure in cells (enoxacin-stimulated fat cells pictured). Enhancing our body’s natural ability to prevent obesity could help tackle a growing health problem, and maybe make next year’s indulgences a little less costly.

Written by Anthony Lewis

Image from work by Andréa Livia Rocha and colleagues

Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil

Image copyright held by the original authors

Research published in Science Advances, December 2020

Blood Vessel Blocker

As a tumour grows its need for a blood supply drives certain cells in the tumour to form blood vessels. Now, researchers have found a microRNA – a tiny RNA that regulates gene activity – that inhibits such vascularisation and might therefore help prevent tumour growth. These images show endothelial cells (red) – the type that line blood vessels – growing on fibrous protein beads (for support) in culture. On the left, the cells are growing normally, with some of the cells forming sprouting structures equivalent to developing blood vessels. On the right, however, the cells have been treated with the microRNA and sprouting is suppressed. In tumours, high levels of this RNA was associated with better patient outcome, while in mice, boosting levels of the RNA prevented tumour growth. These results pave the way for further development of this tiny molecule and its potential addition to the oncologists’ treatment toolbox.

Written by Ruth Williams

Image from work by James V. McCann and colleagues, Dudley Lab UVA School of Medicine

Department of Microbiology, Immunology, and Cancer Biology, The University of Virginia, Charlottesville, VA, USA

Image copyright held by the original authors

Published in the Journal of Clinical Investigation, March 2019

High-tech Heart Gel

Because adult heart cells have almost no capacity for replication, muscle damage caused by a heart attack is largely irreparable, causing life-long heart weakness. Certain microRNAs – small, gene-regulatory molecules – have been shown to encourage heart cell replication and improve heart function in mice. But because RNAs degrade rapidly after injection, repeated treatments are necessary for them to be effective. To sustain microRNA activity for longer, scientists have now engineered a novel microRNA-containing hydrogel (a mix of polymers and water) that acts like a liquid as it passes through the syringe needle, but returns to a firm gel state once injected into the heart. As such, the microRNAs are stuck in place, protected by the gel and are released slowly as the gel degrades. Indeed, a single injection has been show to sustain heart cell replication (red dots) in mice for two weeks and improve heart function within a month.

Written by Ruth Williams

Image by Leo L. Wang and colleagues. Department of Bioengineering.

University of Pennsylvania, Philadelphia, PA, USA

Image copyright held by the original authors

Research published in Nature Biomedical Engineering, November 2017