Tuesday, November 15, 2011
The case of "junk DNA" and why it shouldn't be called junk: RNA.
This is part 5 of 5 in a series dedicated to the concept of "junk DNA". Links to the previous parts: Part 1, Part 2 (redundancy), Part 3 (epigenetics), and Part 4 (topology).
I recently discovered the work of John S. Mattick (who's written many beautiful reviews on RNA) and learned a new concept, which he discusses in : while the number of protein-coding genes is relatively constant across complex species, non-coding DNA increases with developmental complexity.
Isn't it intriguing? You see, when it comes to DNA people tend to think that everything revolves around genes. They are the bits of DNA that get transcripted into coding RNA from which proteins are made. However, as I have stated in my previous "junk DNA" posts, most of our DNA is non-coding -- it doesn't yield proteins. Well, it turns out, RNA transcripts from non-coding DNA are highly expressed during embryogenesis and in the brain, and they are involved in regulating epigenetic processes. They don't code proteins but they do have a function, and in fact, that's why they are called non-coding functional RNAs (which almost sounds like an oxymoron).
In , Mattick and colleagues list examples of non-coding RNA that was later identified to encode a functional protein (in a different context), and they hypothesize that this may be the case for many more non-coding RNA regions, as they may be "translated in very specific contexts or at very low levels." The opposite may be true for coding RNA, in other words, it could be that coding RNA also holds non-coding regulatory functions in other contexts. They conclude with an interesting analogy with cell phones, which were originally created to fulfill the need to communicate in the absence of landline and then gradually evolved into calculators, internet browsers, cameras, and media players. Similarly, they hypothesize that RNA has gradually acquired many numerous functions over the course of evolution, building a very complex platform for genetic innovation.
All this suggests that DNA alone is only one part of the picture, and together with DNA, we should be sequencing RNA as well to see whether or not putative mutations are indeed expressed. In fact, this has been done in a recent study in plants [doi:10.1038/nature10414], paving the way for future human studies as well. (Sequencing both RNA and DNA was indeed discussed in this wonderful post from Genomes Unzipped, together with the challenges that sequencing and aligning both DNA and RNA poses.)
 Mattick JS (2011). The double life of RNA. Biochimie, 93 (11) PMID: 21963144
 Dinger ME, Gascoigne DK, & Mattick JS (2011). The evolution of RNAs with multiple functions. Biochimie, 93 (11), 2013-8 PMID: 21802485