Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Red blood cells have a tiny but effective protector -- microRNA

Genetic molecules resist chemical stress, may have wider roles

Pediatric researchers have discovered a new biological pathway in which small segments of RNA, called microRNA, help protect red blood cells from injury caused by chemicals called free radicals. The microRNA seems to have only a modest role when red blood cells experience normal conditions, but steps into action when the cells are threatened by oxidant stress.

Led by hematologist Mitchell Weiss, M.D., Ph.D., of The Children's Hospital of Philadelphia, the current study describes how a particular microRNA fine-tunes gene activity by acting on an unexpected signaling pathway.

The study appears in the August 1 issue of the journal Genes & Development, simultaneously with a similar study of microRNAs and red blood cells by a University of Texas team led by Eric Olson, Ph.D. The two studies reinforce each other, said Weiss.

MicroRNAs are single-stranded molecules of ribonucleic acid (RNA) averaging only 22 nucleotides long. Scientists estimate that 500 to 1000 microRNAs exist in the human genome. First characterized in the early 1990s, they received their current name in 2001. Over the past decade, scientists have increasingly recognized that microRNAs play a crucial role in regulating genes, most typically by attaching to a piece of messenger RNA and blocking it from being translated into a protein, but many details remain to be discovered.

"Although microRNAs affect the formation and function of most or all tissues, for most microRNAs, we don't know their precise mechanisms of action," said Weiss. "In this case we already knew this microRNA, called miR-451, regulates red blood cells in zebrafish and mice, and because it is highly conserved in evolution, we presume it operates in humans as well. But its functional roles were poorly understood."

By investigating how microRNAs influence red blood cell development, Weiss and colleagues aimed to understand how such development goes wrong in hemolytic anemia, in which red blood cells are destroyed in large numbers, or in disorders of abnormal blood cell production. The current study used knockout mice—bioengineered animals in which the miR-451 gene was removed and could not function.

They found that preventing the activity of miR-451 produced only modest effects—mild anemia in the mice—but when the team subjected mice to oxidant stress by dosing them with a drug that produces free radicals, the mice had profound anemia. The oxygen radicals attacked hemoglobin, the iron-carrying molecule in red blood cells.

"This is a common theme in microRNAs—frequently, they don't play a central role during tissue formation or normal conditions, but they have a strong protective effect when an organism is stressed," said Weiss. "Over evolutionary time, red blood cells have evolved ways to protect themselves; one of those ways is the action of microRNA."

Weiss's team found that miR-451, acting through intermediate steps on a signaling pathway, affects a key protein, FoxO3. As a transcription factor, FoxO3 regulates hundreds of genes; in this case, FoxO3 stimulates specific genes that protect red blood cells from oxidant stress. The knockout mice in this study, having lost miR-451's function, showed impaired FoxO3 activity, and less ability to protect their red blood cells.

The regulatory pathway seen here, Weiss added, may have medical implications beyond blood cell development. "This finding does not have immediate clinical application for patients with blood diseases, but it sheds light on how microRNAs fine tune physiological functions in different contexts," said Weiss. FoxO3 regulates anti-oxidant functions in heart cells and also acts as a tumor suppressor, so miR-451 may have an important role in heart protection and in fighting cancers. "Further studies may broaden our knowledge of how this microRNA may defend the body against disease," he added.

The National Institutes of Health, the Roche Foundation for Anemia Research and the March of Dimes Foundation provided grant support for this study. Weiss's co-authors included Barry H. Paw, M.D., Ph.D., of Brigham and Women's Hospital and Harvard Medical School; Duonan Yu, Camila O. dos Santos, and several other colleagues from The Children's Hospital of Philadelphia; and collaborators from Northwestern University, Chicago; Mount Sinai School of Medicine, New York City; and the Amnis Corporation, Seattle.

"miR-451 protects against erythroid oxidant stress by repressing 14-3-3zeta," Genes and Development, published online July 31, 2010, in print issue on Aug. 1, 2010. doi: 10.1101/gad.1942110.

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 460-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit

John Ascenzi | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Make way for the mini flying machines
21.03.2018 | American Chemical Society

nachricht New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Make way for the mini flying machines

21.03.2018 | Life Sciences

Taming chaos: Calculating probability in complex systems

21.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>