Why LncRNAs?

99% of our genome is composed of a vast and unexplored wilderness of non-coding DNA. Within this wilderness are many thousands of poorly-understood genes termed “long non-coding RNAs”, or lncRNAs.

As their name implies, lncRNAs are long RNA molecules that are unusual because they do not apparently encode any protein. It is this property (or lack of property) that distinguishes lncRNAs from the well-known messenger RNAs that are described in the Central Dogma of molecular biology. mRNAs serve only to specify the production of protein. In contrast, it is thought that lncRNAs are intrinsically functional RNAs, either through their sequence or their structure.

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From available evidence, it would appear that lncRNAs play diverse roles in the cell, from the regulation of chromatin structure and gene transcription, to controlling mRNA stability and translation, to forming components of cellular structures. Several lncRNAs are known to play central roles in fundamental biological processes, exemplified by the essential X-chromosome silencing RNA, XIST. It is thought that lncRNAs, similar to proteins, are modular molecules that are composed by several independent domains. These domains are capable of interacting with protein, RNA and DNA, making lncRNA versatile regulators within the cell.

The first lncRNAs were discovered in the 1990s, and since then researchers have catalogued tens of thousands of these enigmatic genes in humans alone. Some lncRNAs are conserved through hundreds of millions of years of evolution, while others appear to arise rapidly and may help drive species-specific traits.

Why study lncRNAs?

The total number of lncRNAs in our genome remains unknown, but we suspect that it may lie in the region of 50,000 to 100,000. This is an enormous number of genes. For comparison, the number of protein-coding genes is 20,000. To date, researchers have investigated <400 lncRNAs, meaning that probably 99% of lncRNAs are completely unknown.

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The reason we should study these genes is that they represent a vast potential genetic space that may explain human diseases, as well as unique human traits such as cognition. There is already compelling evidence that lncRNAs play key roles in many cancers, which were unknown until <5 years ago.

Therefore, the study of lncRNA offers an exciting opportunity to understand disease. However the massive number of these genes, as well as their unique properties, introduces new scientific challenges, and makes it necessary to develop novel approaches and hypotheses.