• John Rinn

Putting the RNA in lncRNA using genetics.

Since the sequencing of the human genome a potential new class of genes emerged termed long noncoding RNAs. Although these "noncoding" regions of the genome produce RNA --- a major question is does the RNA do anything?

Many studies have pointed to the underlying DNA as the key elements or these just being accidents the cell made. This has been a very difficult question to address and the source of many debates.

However ultimately "genetics is to biology as math is to physics" meaning genetics is in a way the mathematical proof of biology. So we can address the controversy using genetics or math that most would agree on.

Thus, the ultimate test would be removing the genetic material (or DNA) that encodes a lncRNA gene from a mouse -- and then replacing the RNA on a different chromosome altogether. If something goes wrong when we remove the lncRNA genetic material and we can fix it with RNA coming from somewhere else -- we can definitively conclude the molecular activity is the RNA and not DNA.

Here Jordan Lewandowski and colleagues took away the entire lncRNA locus for FIRRE (even it's promoter -- or front lawn if you will). They found that these mice are defective in making blood stem cells (hematopoiesis). When they restored the RNA in the mice that no longer had the FIRRE DNA -- they were fixed and had a happy immune system again! Interestingly, if they turn up the amount of FIRRE RNA in the animals they die in response to the simplest of infections. It's like the three-bears: too-little FIRRE is to cold, too-much FIRRE to hot and somehow our bodies now how to keep the FIRRE just right.

Overall, this study definitely shows, using genetics, FIRRE RNA has an important role in the immune system and perhaps other complex tissues and organs -- i have my eye on the FIRRE in the brain!

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