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The Theme of Regulation in Eukaryotes

Thirty percent of the transcription happening in one of your cells (right now) produces mRNAs, or messenger RNAs, that code for proteins. The other seventy percent? Those are called noncoding RNAs, or ncRNA, because they don't get turned into protein.

That's a big chunk of RNAs.

These RNAs include transcripts like tRNAs and rRNAs. However, it also includes RNAs that have crazy regulatory roles in your cell, contributing just as much function as proteins.

Wanna hear about one?

Some of your cells produce a really long ncRNA that is full of bologna. For that reason, it's been named HOTAIR.

Kidding. HOTAIR is short for HOX Antisense Intergenic RNA. It's a piece of RNA that is transcribed from a HOX gene cluster, which are genes involved in development. It's transcribed in the opposite direction as the HOX genes, which is why it's called "antisense." The word intergenic refers to the fact that it's between genes.

Normally, transcription factor proteins regulate the activity of RNA Polymerase. These proteins bind the DNA or each other, resulting in the increase or decrease of gene expression. As an RNA, HOTAIR is able to bind to some transcription proteins and regulate their function, just like a protein would. For a long time, scientists didn't know that RNA had those kinds of superpowers.

It's like the RNA is saying to some proteins, "Come on down! The DNA is fine." The recruited protein transcription factors then take the "okay" signal, arriving at a specific chromosome location to modify its chromatin, or combo of nucleosomes and DNA. Without HOTAIR, some genes would be turned on, or expressed, when they should be silenced. Shhhh.

HOTAIR was the first ncRNA found to affect DNA on a one chromosome while being transcribed from a different chromosome.

This looks like a pair of eyeglasses, but it's actually a secondary structure of the HOTAIR ncRNA, which can basepair with itself to create a non-linear shape. The colors represent the sequence conservation among HOTAIR RNA. The more red, or conserved a nucleotide, the more important it might be to its function and interaction with other proteins or nucleic acids.

HOTAIR is so important that it's no surprise its misregulation has been associated with cancer. In fact, scientists are beginning to understand how they can use the expression of HOTAIR and other ncRNAs to characterize cancer prognosis and possible treatments. For example, HOTAIR is transcribed at REALLY high levels in breast cancers that are advanced, compared to breast cancers in earlier stages.

Pretty handy for a little RNA, right? Although HOTAIR functions to repress some specific genes, it's just one of many ncRNAs that can regulate genes and proteins in all different ways. New ones are being uncovered all the time, quickly becoming crowned as a previously underappreciated yet super important way to regulate biological function.

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