Linking lncRNA to autoimmune diseases

News Medical Life Sciences – An interview with Dr. Chase Spurlock, CEO, IQuity, conducted by April Cashin-Garbutt, MA (Cantab)

What are long non-coding RNAs (lncRNAs) and how do they differ from messenger RNAs (mRNAs)?

Well, the central dogma of biology states that DNA makes RNA and RNA makes proteins. However, there are many different types of RNAs, and only one of them, the messenger RNA (mRNA), gives rise to proteins. Some others don’t make proteins at all.

When the maps of the human genome were completed, it was noticed that there were stretches of DNA sequence for which no function had been identified. We called these regions “junk DNA.” But over a decade later, we now appreciate that this “junk” is in fact exerting some sort of biological function, and one way is through the production of long non-coding RNAs, or lncRNAs.

lncRNAs emerged as a new class of RNA molecule predominantly in the late 2000s and we’re still trying to fully recognize their importance. lncRNAs don’t give rise to proteins, but they’re powerful regulators of other genes that are often nearby.

Why is IQuity researching into lncRNAs?

IQuity has been interested in lncRNAs because many of the protein-coding genes, the mRNAs — which are important in the immune system, and play important roles in mounting an effective immune response — have lncRNAs in close proximity. So our curiosity led us to consider a guilt-by-association strategy. We began to chart our research in this area looking for co-expressed lncRNAs and nearby mRNAs that we knew to be important.

We studied whether these lncRNAs were influencing the genes next door, and if so, if we could modulate a lncRNA to alter a cell’s function or phenotype. The answer was yes. So then the next question was, could these lncRNAs be knocked down to treat autoimmune diseases or diseases of the immune system? We’ll need a little more time to figure that one out.

In the meantime, we’ve investigated the expression of known lncRNAs and those we’ve identified ourselves, trying to see if they have altered expression levels in diseased and non-diseased patients. What we found is that differences in lncRNA expression levels among our patient populations far exceed anything we’ve ever observed with mRNAs, so we’ve started to explore lncRNAs in greater detail and will continue this work in the future.

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