Epigenetics:
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The non-coding RNA is emerging as a fully functional molecule competing with proteins. Separate but equal.
These non-coding RNAs are present throughout the genome. Some come from introns. Initially, it was assumed that the parts of the messenger RNA that were cut off from the introns during the supply were destroyed. It is now highly probable that some (if not all) of these parts are processed and converted into functional non-coding RNA. The rest of the genes overlap and transcribe from the strand in the other direction. And some are present in parts where no protein coding gene is present.
We have already mentioned two non-coding RNAs. These are the Xist and Tsix that are needed to disable the X chromosome. When Xist was first identified, it was the second name coding RNA until then. According to current estimates, there are thousands of such molecules in mammals. There are over 30,000 long non-coding RNAs in mice alone. These long non-coding RNAs are actually longer than protein coding messenger RNAs.
In addition to inactivity, non-coding also plays an important role in RNA printing. Many imprinted parts contain a region that encodes long non-coding RNA and mutes the expression of surrounding genes. It's just like the Xist effect. The copy of the chromosome that expresses the long non-coding RNA is silenced by the messenger RNA encoding the proteins. For example, there is a non-coding RNA called Air which is expressed inside the placenta and inside the mice comes from the paternal chromosome number eleven. The gene present with air expression suppresses Igf2r but on the same chromosome. This mechanism ensures that the Igf2r gene is only transmitted by the mother.
This Air-coded RNA helped scientists understand how these long non-coding RNAs suppress gene expression. Non-coding RNAs are located within a specific portion of the imprinted gene cluster and act as a magnet for an epigenetic enzyme G9a. G9a puts a represi- tive mark on the H3 histone protein inside the nucleosome in this part of the DNA. This histone modification creates a repressive chromatin environment that turns off the genes.
The discovery helped epigenetics find the answer to a question that had been bothering them for some time. How do enzymes that modify histone that insert or remove epigenetic markers come together in the genome? Houston-modifying enzymes cannot directly identify specific parts of the genome. Then how do they get to the right part of the genome?
Houston modification patterns are present on different genes in short-lived cells. For example, an enzyme EZH2 methylates the amino acid lysine present in histone H3 at position 27 but it targets another histone H3 in another cell. Simply put, it will methamphetamine the histone proteins on gene A in white blood cells, but not in nerve cells. Similarly, it will sweeten histone on gene B in nerve cells but not in white blood cells. It is the same enzyme in both cells but it is being targeted differently.
There is evidence that the targeting of some epigenetic modifications can be elucidated by interaction with long non-coding RNA. Jenny Lee and her colleagues have researched a non-coding RNA that binds to a protein complex. This complex is called PRC2 and it creates repressive histone edits on the histone. PRC2 contains many proteins and the one that interacts with non-coding RNA is probably EZH2. The researchers discovered that this complex is actually linked to thousands of long non-coding RNA molecules in the embryonic stem cells of mice. These non-coding RNAs act as bait. They can attach to a specific part of the genome where they are made and then pull repressive enzymes to turn off the expression of the gene. This is because repressive enzyme complexes contain proteins such as EZH2 that are capable of binding to RNA.
Scientists like to come up with new theories, and somehow a better theory could be formed around non-coding RNA. They seemed to connect to the part from which they were transcribed and turned off the expression on the same chromosome. But if we go back to the example given at the beginning of this chapter, we have to say that it is becoming clear that we have managed to build a small shed and have already put a lot of debris on the roof.
There is a family of amazing genes called HOX genes. Mutations in these genes inside fruit bees reveal incredible phenotypes, such as the legs protruding from the head. A long uncoding RNA HOTAIR that regulates a gene region called a HOX-D cluster. This HOTAIR also binds to the PRC2 complex and forms a chromatin region marked with the represen- tion of the histone. But HOTAIR does not transcribe from the HOX-D position of chromosome number twelve. Rather, chromosome number two encodes every existing HOX-C gene cluster. No one knows why and how HOTAIR connects to the HOX-D position.
A similar puzzle exists with reference to the most studied non-coding RNA Xist. Xist noncoding RNA spreads throughout the inactive chromosome but we do not know how. RNA molecules do not normally cover chromosomes. There is no apparent reason why non-coding RNA can do this, but one thing is for sure, it has nothing to do with chromosome sequencing. The experiments mentioned earlier (in which we saw that Xist is capable of disabling the entire auto-som as long as it has an X-in activation center) show that when Xist attaches to a chromosome then it Keeps traveling on it. Scientists are still amazed at the potential of this most widely studied non-coding RNA.
Another surprise is that until recently, all long non-coding RNAs were thought to suppress gene expression. In 2010, Professor Ramin Sheikhatar identified more than 3,000 long non-coding RNAs in many types of human cells. These long non-coding RNAs were exhibiting different expression patterns in different types of human cells, indicating that they have a specific role. Professor Sheikhatar and his team tested some non-coding RNAs to determine their functions. And the results were unexpected, as fifty percent of the non-coding RNAs were amplifying and suppressing the expression of neighboring genes.
We do not know how noncoding enhances RNA gene expression. This study makes it clear that we still know very little about long non-coding RNA. So we have to be careful before we make a new scientific belief.