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Post-transcriptional regulation

Video transcript
Voiceover: Let's talk about post-transcriptional regulation which is regulation basically once DNA has been transcribed into mRNA and I've drawn out this little schematic for you here and it kind of just shows you how a DNA strand has a corresponding RNA strand and then the mRNA strand afterwards and I'll sort of explain what all the different colors and words mean in just a little bit. So once DNA is transcribed by RNA polymerase into the corresponding RNA strand, this RNA strand needs to get what I call a tidy little haircut and then don some protective outerwear before it can leave the comfort of the nucleus for its big debut into the cytoplasm in the form of a fully processed messenger RNA or mRNA strand. Now keep in mind that this form of regulation occurs in eukaryotes only and this modification also helps to stabilize the mRNA to protect it from premature degradation before it gets translated into a protein. So as you can see here, DNA gets transcribed one to one, base for base, into RNA and you can see here that there are sections of the RNA that ultimately make it into the finished mRNA, these short segments, which are turned exons, and they are the sequences that code for the ultimate protein product. And then there are short non-coding segments of RNA that get cut or spliced out and this would be the haircut that I alluded to earlier and so these are called introns, and this is accomplished by a large molecular entity called the spliceosome. So the spliceosome binds on either side of an intron, loops the intron into a circle, and then cleaves it off, and then ligates the two cut ends of the exposing exons together, kind of cinches them together. And an easy way to remember which sequences are exons, which ones are introns, is that exons exits the nucleus and introns stay in the nucleus so exons kind of stands for exit. Now even though the mRNA has gotten its nice little haircut, it's not quite ready to leave the nucleus just yet. It has to grab what is called a 5' prime cap and a 3' prime poly-A tail. Now what are those things that I just mentioned? So a 5' prime cap refers to changes at the 5' prime end of the mRNA and remember that this is the phosphate end of the nucleotide bases in the mRNA and some people like to remember this as F for five prime and for fosphate so that's how you can kind of keep the two ends straight. And capping at the 5' prime end converts this end of the mRNA to a 3' prime end by a 5' prime to 5' prime linkage which basically just protects the mRNA from exonucleases which degrade foreign RNA. The cap also promotes ribosomal binding for translation and also helps the regulation of nuclear export of the mRNA. Now the poly-A tail, that goes on the other end, the 3' prime end of the mRNA which has the terminal hydroxyl group and so what do I mean when I say poly-A tail? Well, poly-A tail refers to polyadenylation in which multiple adenosine monophosphates or basically adeonine bases are added to act as a buffer for exonucleases in order to increase the half life of mRNA and again, protect it from degradation. And so the purpose of the poly-A tail is really very similar to the 5' prime cap which is basically to protect from degradation, help with promoting translation, and regulating nuclear export. The poly-A tail also does one more thing and it kind of just helps with transcription termination for the RNA polymerase that's transcribing the messenger RNA. Polyadenylation is catalyzed by an enzyme called polyadenylate polymerase which as the adenosine monophosphates using adenosine triphosphate as the substrate and the poly-A tail is built until it's about 250 or so nucleotides long. So overall the 5' prime cap and the poly-A tail help to stabilize the mRNA for translation. That's the key point to take home from here. So once the mRNA has donned its cap and tail and had its introns spliced out, its now ready to exit the nucleus to be translated into a protein. Now additionally, there's one more type of RNA regulation called RNA editing, which is a process that results in seqeuence variation in the RNA molecule and is catalyzed by various enzymes. RNA editing is relatively rare and these events may include insertion, deletion, and base substitution of nucleotides within the edited RNA molecule. Now one of these enzymes is called adenosine deaminase acting on RNA or ADAR enzymes which convert specific adenosine residues to inosine in an mRNA molecule by hydrolytic deamination. Another type of editing is called cytosine deaminase acting on RNA, or CDAR, which involves deamination of cytosine to uridine by cytidine deaminase. RNA editing is currently being extensively studied in relation to infectious diseases because the editing process alters viral enzymes and their function so kind of an exciting, new emerging concept in post-transcriptional regulation.