Not junk RNA after all

25 June 2019

Non-coding RNA was once considered junk. Now it has been found to play an important role in ensuring accuracy in cell division and chromosome segregation in a significant discovery by Dr Karen Wing Yee Yuen (Croucher Fellowship 2008) and Dr Yick Hin Ling, both at the University of Hong Kong (HKU).

Each person’s genetic code is stored in chromosomes composed of DNA. To maintain the accuracy of this code in all cells, chromosomes have to be distributed equally to the two daughter cells formed during cell replication. Otherwise, cells with an abnormal number of chromosomes may cause spontaneous abortion, genetic diseases, or cancers.

The centromere, a region of DNA that directs chromosome movement during cell division, is an important element for such chromosome segregation. In a recent breakthrough, Yuen and Ling found centromeric DNA is used as a template to produce a non-protein coding centromeric RNA essential for chromosome stability. With either too much or too little centromeric RNA (cenRNA), the centromere will be defective and chromosomes lost.

The findings have been published in Proceedings of the National Academy of Sciences of the United States of America (PNAS)

Our DNA has the code for about 20,000 proteins. To produce a particular protein, such as insulin, the DNA segment that codes the protein has to be used as a template to copy it into an RNA molecule. That RNA then serves as a recipe for directing the cells to make the specific protein.

Only two per cent of our DNA is protein-coding. Yet, 70 per cent is still copied into RNAs, which are not recipes to make proteins and are known as non-coding RNA. These non-coding RNAs used to be considered “junk”. However, recent research has revealed that non-coding RNA actually carries out some vital roles, such as gene regulation and maintenance of chromosome structure. The HKU findings add to these functions.

While the HKU study was performed using baker’s yeast, a single-cell organism, non-coding RNA copied from the DNA of the centromere was also found in multicellular organisms such as humans, mice and flies, Yuen said. This suggests that “centromeric RNA (cenRNA) is a fundamentally important molecule that is commonly used by nature to control cell division”, she explained.

“The mechanism of cell division is strikingly similar in many forms of life. These little organisms [such as yeast] allow us to do experiments that are difficult to perform in humans or mammalian cells,” noted Yuen, who leads HKU’s Chromosome Biology Laboratory.

Many applied clinical studies began by studying the cellular processes in these model organisms. Important cell biology research using yeast was awarded the Nobel Prize in Physiology or Medicine in 2013 and 2016.

Postdoctoral fellow Ling is part of Yuen’s lab team and first author of the study. “Recent research shows abnormally high expression of centromeric RNA in some cancers, such as ovarian cancers,” Ling said. “Mis-regulation of cenRNA in the cell might contribute to cancer progression. Further study is required to test this.”

In terms of disease diagnosis and therapies, Ling said: “We will try to see if cenRNA could be used as a cancer biomarker. If the cancer cells release a high level of cenRNA to the blood, it could be used for early detection or for monitoring the malignancy of the tumour.”

Dr Karen Wing Yee Yuen completed her PhD in the Department of Medical Genetics at the University of British Columbia, Canada, studying chromosome instability in budding yeast Saccharomyces cerevisiae, and human cancers. She then received a Croucher Fellowship in 2008 to pursue postdoctoral training at the Ludwig Institute for Cancer Research and University of California, San Diego, US, studying centromere and kinetochore formation and propagation in Caenorhabditis elegans (C.elegans). She is currently an Assistant Professor in the School of Biological Sciences at the University of Hong Kong.

To view Dr Yuen’s Croucher profile, please click here