Regulation of Gene Expression Part 3

Welcome to the last part of the regulation of gene expression series! In this page, we will talk about ncRNAs, miRNAs, siRNAs, piRNAS, RNAi, and their effects on the cell. As you can see, this whole page is related to RNA, so prepare yourself. Let's get straight into it :)

Protein coding genes only make up a small portion of the amount of genes in the human genome. But, according to studies, around 75% of the human genome is translated in a cell at some point in their lives. That means that there's a lot of RNA being translated, but only a bit of it is meant for proteins. So, what is the rest of the RNA doing? Well, some of it includes introns (the untranslated parts of mRNA removed during RNA processing), rRNA, and tRNA, but what is going on with all of that extra RNA left over?

Scientists think much of these genes are transcribed into noncoding RNAs (ncRNAs), or non-protein-coding RNAs. We still don't know a lot about what exactly these do, but we are starting to get a hint. There are a variety of small RNAs that do important functions in the cell, and we think that one of these functions is to help regulate gene expression. While both large and small ncRNAs have shown to regulate at many points in gene expression, we will focus on two types of RNAs today: miRNAs and siRNAs. 

miRNAs, or microRNAs bind to a protein to create a complex, and then bind to complementary sequences in mRNA. They are formed by a longer RNA strand that is cut with enzymes into miRNAs. miRNAs are about 22 nucleotides long. miRNA protein complexes bind to mRNAs, and if 7-8 nucleotides successfully bind, the complex either degrades or blocks the mRNA. We estimate that at least 50% of genes are regulated by miRNAs. 

The second type of molecule is a siRNA, or small interfering RNA. These are similar to miRNAs. siRNAs are like miRNAs in size and use, and they both even utilize the same proteins. The difference between them are just small differences in their precursor molecules (the molecule before it is chopped up). Their precursor molecules are most of the time double stranded RNA. 

When siRNAs block gene expression, the process is called RNA interference, or RNAi. RNAi is used in labs to turn off specific genes to see what they do. We don't know how RNAi evolved, but some scientists think it evolved as a defense against viruses, since RNAi turns double stranded RNA (like the kind many viruses have) into tiny weapons that destroy related RNA. But RNAi affects our own cellular genes, so this might not be true. 

Other than just regulating gene expression, ncRNAs also remodel chromatin. Remember chromatin, that DNA goop pile in the nucleus that ravels into chromosomes during cellular reproduction? I'm talking about that. For example, ncRNAs help form something called heterochromatin (very dense chromatin) at the centromere (the center of the chromosome that holds the sister chromatids together). The area at the centromere has to be loosened to be replicated before being tightened again for mitosis. 

The steps of this process are being debated, but in yeast cells, it basically occurs like this:

1. Centromeric DNA is transcribed into RNA.

2. Each RNA produced from the centromeric DNA is used as a template to form a double-stranded RNA.

3. The double-stranded RNA is broken into siRNAs which form siRNA complexes with proteins.

4. The siRNA complexes bind back onto the RNA being transcribed from the centromeric DNA.

5. The proteins in the siRNA complex call enzymes to modify the proteins in the chromatin (called histones).

6. Chromatin condensation begins, which leads to heterochromatin being formed.

We have no idea how this works with DNA, but our guess is that other ncRNAs are somehow involved. Another thing I mentioned we were going to discuss is piRNAs, which are piwi-interacting RNAs. They were very recently discovered. piRNAs also help with heterochromatin formation by inhibiting transposons (DNA elements that the textbook described as "parasitic"). They're only a tiny bit longer than miRNAs and siRNAs, being around 24-31 nucleotides long. I would continue to describe them a little, but after this, they get really complicated and confusing really fast, and you can't understand without a really solid knowledge on the genome. I will keep in mind to go over them more in a future page, but until now, I will keep it simple as to not confuse people.

By the way, ncRNAs are also involved in turning off the extra X chromosome in females. In a similar process as the one I described above, products of the XIST gene come back to the chromosome and surround and bind to it, which leads to the whole chromosome turning into heterochromatin. 

Now that we've gone through gene expression, you have the background information you need to understand our next topic: Embryonic Development. I am pretty sure I will also have to end up dividing this topic up into different pages like I did this one. It is just too long and too complicated to go over in one small page. Embryonic development, or put simply how cells go from being one singular cell to an entire organism with specialized tissues and organ systems, is the epitome of how amazing gene regulation really is. 

If you're still confused on anything I've mentioned in any of my pages in the Regulation of Gene Expression series, please reach out to me at twisha.sharma30@gmail.com! I am more than happy to answer your questions! That's all I have for you today, though. I hope to see you in the next one!