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Half of the DNA in our cells is derived from repetitive sequences called transposable elements (TEs) that have taken on a life of their own. The defining characteristic of a TE is the ability to copy itself to another place in the DNA, and they have been wildly successful at doing so. Most of the time when this happens, there is no harm done and we live on to reproduce and pass on the new copy to our healthy children. Though usually not harmful, the importance of these sequences to making us human is questionable; accordingly, they have been colloquially referred to as “junk DNA” because their ability to copy themselves means that their presence in the DNA requires no functional explanation. But many researchers, such as my colleagues and I, are undeterred by the junky stench of these regions and have been sifting for buried functions.

The primary reason that much of the genome is referred to as junk is that only 2% of the nucleotides of DNA code for the proteins that do the bulk of the work in the cell. The function of the other 98% is trickier to define, but some of it is called regulatory because it helps turn the expression of the protein coding genes on and off at specific and important times in the life of the cell. These regulatory sequences can be bound by proteins that function in gene regulation to activate or repress nearby genes. Previous studies introduced a surprising and fascinating observation: junk TEs often contain these same regulatory signals! While not every instance of a TE will have regulatory function, enough do that TE insertions appear to be an important mechanism by which gene regulation evolves.

These previous studies examined a specific aspect of gene regulation where a protein binds DNA to activate the transcription of a nearby gene into RNA. In fact, genes are regulated at many different levels, including after their transcription into RNA. Regulatory proteins that bind RNA also exist and influence the RNA’s stability and help move it to the next stage of processing towards being translated into a protein. In a previous paper, my colleagues and I studied the fact that many RNAs contain TEs. Here, we asked whether these TEs in RNA bind regulatory proteins analogous to the case previously found for DNA binding proteins.

It turns out that they do in a big way. Almost all of the regulatory proteins that we examined showed some evidence of binding to TEs in RNA. Numerous well-studied proteins had rampant binding to TEs that had been overlooked until now. Each protein affects the bound RNAs in some unique way, and these repetitive binding sites recapitulated those effects just as well as the non-repetitive, non-junk sites did.

In sum, we found here that TEs can function in RNA as binding sites for regulatory proteins, adding to the growing evidence that the junk of the genome is littered with gems of functional significance. Given the substantial proportion of the human genome covered by these elements, this study and future work will help target our analytical lens on the regions that appear most important so that we can better understand how the human genome works and how it evolved to be this way.

 

Citation:

Kelley, DR, Hendrickson D, Tenen D, Rinn J. Transposable elements modulate human RNA abundance and splicing via specific RNA-protein interactions. Genome Biology (2014), 15:537. http://genomebiology.com/2014/15/12/537

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