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Figure: (Kelley & Rinn 2012)

Human DNA is around three billion nucleotides long, but surprisingly, only 3% of the nucleotides that compose DNA code for proteins, which carry out the bulk of the work in cells. Determining the function of the remaining 97% is a major focus of biological research today, so that we can begin to make sense of the many differences people have in that portion.

Oddly enough, half of those nucleotides are only recently “ours”. They are foreign sequences called transposable elements, that inserted themselves into our genomes from a variety of other sources such as viruses (an interesting area of research in and of itself). Transposable elements have a unique and important property; these sequences are capable of copying and inserting themselves all across the DNA, and their success at doing so explains why they make up so much of the DNA. Because they can just copy themselves without necessarily being connected to a valuable function, the default assumption is that they are useless at best and detrimental at worst, and that the organism would prefer to keep them in check.

Nevertheless, once in the DNA, transposable element sequences do have the potential to become functional and contribute more to the organism than just self-replication. In an evolutionarily competitive world, organisms must be resourceful and use every opportunity they can to better survive and propagate. Thus, there are some examples of the genome making use of these transposable elements for important tasks within cells. But how wide this phenomenon spreads is unknown.

In parallel, researchers have recently noticed that proteins are not the only genetic material that does work in the cell. RNA, a molecule previously thought to exist mainly as an intermediate state between the DNA creating a protein, has now been found to be an active part of some cellular tasks. RNA is related in structure to DNA, but rather than forming the iconic double helix, it exists as a single strand. These single-stranded RNAs are copied from genes in the DNA, and some types can move around the cell to do work.

Here, John Rinn and I added to the growing list of functional transposable elements with the discovery of a class of hundreds of RNAs that were created from mutated instances of a specific family of transposable elements called human endogenous retrovirus H (HERVH). These genes are turned on only in our stem cells, an unintuitive place. Stem cells represent a powerful stage in development where the instructions to form every cell type in the body is maintained and organized, so they can be properly applied across development. We recognized many of the signals of stem cell gene regulation in the HERVH sequences, suggesting they may have a valuable role in early development. HERVH is a relatively new entrant to our DNA, having inserted many hundreds of times over the course of the primate lineage, some of which have evolved to form these functional RNA genes. Thus, this represents an enticing example of a genetic phenomenon specific to humans, and perhaps our recent ancestors.

How do stem cells, which are so critical in our development, make use of HERVH-RNAs? And can this system serve as a model to find additional examples of how the genome may shape its fascinating foreign half, filled with transposable elements and long noncoding RNAs, into important functions? Future work will be needed to answer these exciting questions.

Citation:

Kelley, D. & Rinn, J. (2012). Transposable elements reveal a stem cell-specific class of long noncoding RNA. Genome Biology. 13:R107. http://genomebiology.com/2012/13/11/R107

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