LincRNA discovery could lead to targeted treatments

Our genetic code includes more than 15,000 specific sections that can be made into molecules called lincRNAs. Some of these parts can occur in circular parts of our genome called topological association domains, or TADs.

The lincRNA derived from TAD appears to act as a marker indicating a specific tissue type within it. When things go wrong with this network, markers can help with targeted medical interventions. The team that invented this novel feature have outlined ways to apply this idea to a variety of diseases, and demonstrated it with a heart disease known as hypertrophic cardiomyopathy.

Diseases can affect very specific tissues in our bodies, but current treatments often don’t discriminate in the areas they affect. For this reason, many studies in the field of medicine have led to more targeted treatment. One avenue of research lies in exploring a relatively recently discovered section of the genetic code called long intergenic noncoding RNA, or lincRNA. The regions of our genome where lincRNAs are copied, or transcribed, were once referred to as junk DNA, but a growing body of research shows that they are not.

“Recently, I felt compelled to uncover what makes lincRNA different from the more familiar messenger RNAs, which are used to make, or express proteins,” said Yu Servant of the Tsunoda Laboratory in the University of Tokyo’s Department of Biological Sciences.

LincRNA in our genome. The genome can be thought of as a long string of genetic information, in which some parts are rolled up into a structure called TAD. In this section, some of the subsections that are transcribed into lincRNAs can indicate the specific networks they contain. When these markers show something abnormal, this may in turn indicate whether that particular tissue is suffering from a disease. Image/Servant et al

LincRNA controls biological processes

“I want to comprehensively describe the mechanisms that explain the differences in expression specificity between RNA types. While messenger RNAs need to synthesize proteins, lincRNAs can function without making proteins and appear to be much more specific about what they express. Through the expression of different molecules, lincRNAs control many different biological processes, such as the activity of certain genes, and when expression is erroneous, it can indicate disease.”

Servant and his team explored the way some of the 15,000 known lincRNAs are expressed. Their findings confirm previous observations that lincRNA expression is much more dependent on the tissues containing it, than expression of messenger RNA. But more interestingly, the researchers also found that this specificity was further enhanced by which part of the lincRNA genome came from.

LincRNAs transcribed from circular TADs are much more likely to result in tissue-specific expression than are lincRNAs from outside this region.

“Armed with the knowledge of where to look for these highly tissue-specific lincRNA markers, we propose an analytical framework for interpreting the properties of lincRNAs as indicators for different tissues,” said Servant.

“As an experiment, we have applied our framework to hypertrophic cardiomyopathy (in which the heart muscle thickens) and discovered what causes the abnormal expression of the keratin protein that causes the disease. My hope is that now we can explore this area further and find some of the underlying abnormal expression products that might lead to things like tumors.”

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