Often it takes scientists time to understand the true function of some biological structure that may at first appear purposeless, perhaps even pointless. White matter in the brain, for instance, was long thought to be merely passive tissue, especially when compared to the seemingly more vital gray matter, but now it is known that white matter actively coordinates communication within the brain. Similarly, small non-coding RNAs, which are chaotically distributed throughout a cell, were simply thought to be "transcriptional noise," in the words of Dr. Steven Jones, a professor at Simon Fraser University and the University of British Columbia. After all, scientists could never assign them an actual function or see their connection to any disease. Now, though, Jones and his colleagues have discovered that small non-coding RNAs can be used to predict whether an individual has breast cancer and even more, these molecules may even predict survival outcomes for patients. "By using a computational approach to analyze small RNA sequence information … we have been able to filter through this noise to find clinically useful information," Jones stated in a press release.

RNA 411

RNA strands are continually made, broken down, and then repurposed for another job. RNA, or RiboNucleicAcid, is a molecule with long chains of nucleotides. The RNA nucleotide has a phosphate backbone and four nitrogen-containing biological compoundsadenine, guanine, cytosine, and uracil which are bonded together with a ribose sugar at the end. The sugar acts as the connection point, linking the chains together.

The main job of RNA is to serve as DNA’s messenger, transferring the instructions (or genetic code) from the DNA hidden within the nucleus of a cell. Simplistically, DNA instructs RNA to make protein. The actual process, though, is more complex and not so one-directional. Nevertheless, after being made by and receiving instructions from the DNA, the RNA carries this to structures called ribosomes, which then makes the intended protein. The whole point of this process, scientists believe, is to prevent the DNA from having to leave the nucleus. Somewhat like a queen bee within a hive, then, the DNA is protected from damage by the RNA which like the worker bees, carries out the actual work of cellular processes.

While DNA is usually found in a double-stranded form in cells, RNA is typically found in a single-stranded form that allows it to fold itself into complex, 3D structures this morphing ability is what allows it to take on a variety of jobs and activities. Generally, RNA molecules synthesize protein, which perform various catalytic and structural assignments within the cell, and sometimes transmit genetic information. Small non-coding RNAs are RNA molecules that do not make proteins and because they seemed so purposeless, they have puzzled many a scientist. Now, though, one team of researchers may have discovered a new way to read these molecules.

Not Just White Noise

“Small non‐coding RNAs (smRNAs) are known to be significantly enriched near the transcriptional start sites of genes,” wrote the researchers in a summary of their research that appears in EMBO Press. For this reason, then, the researchers took a closer look at the transcriptional start site, where the process of DNA instructing RNA to make protein begins, and discovered a difference between smRNAs in healthy individuals and patients with breast cancer (in this case, breast invasive carcinoma) essentially, they could tell them apart, could distinguish between smRNAs from health people and cancer patients. Next, the team mapped these RNA molecules to specific locations on the DNA sequence and looked for a relationship between how strongly the non-coding RNAs expressed themselves and the disease status of the patients. Next, the researchers tested to see if the expression of the small RNAs in specific locations could be used to predict the presence of disease in another group of tissue samples.

The test accurately and efficiently predicted the correct disease status for the samples in the new study group. "Further work is required but based on our data we believe there is considerable diagnostic potential for these small non-coding RNAs as a predictive tool for cancer," Jones said. He added that with more research, this class of small non-coding RNAs may also be found to be useful in predicting the existence of other types of cancer or disease.


Source:  Zovoilis A,  Mungall AJ, Moore R, et al. The expression level of small non-coding RNAs derived from the first exon of protein coding genes is predictive of cancer status. EMBO reports. 2014.