When scientists sequenced the human genome (our full genetic “blueprint”) they were surprised at how few actual genes (individual genetic “recipes” for things like proteins) we had (many a bet was lost!) To understand what was going on, I need to introduce you to the intron!
blog form: bit.ly/altsplicing
We keep the original version of our genome in DNA. But when we want to make a protein, our cells first have to make an RNA copy of that DNA through a process called transcription. The RNA produced is called messenger RNA (mRNA) because it serves as a molecular messenger, taking that protein recipe to the “chefs” - protein-making complexes called ribosomes. At first glance, this may seem like a waste of time, energy, and resources but there are several benefits. I will go into a bit more detail but here’s an overview to tide you over
- DNA protection: that original DNA version is precious - mess with it in one cell and you can get mutations that are carried onto all further cells born from that cell - so it is kept safe in a membrane-bound compartment inside the cell called the nucleus. But the ribosomes are in the cytoplasm (the general cellular interior) - so making mRNA copies that get exported out of the nucleus and into the cytoplasm allows the DNA to stay put but protein to still be made
- amplification: you only have 2 copies of a gene (you get one from each parent, except for the sex-chromosomally-located ones), but you can make “as many” mRNA copies as you want. And there are a LOT of ribosomal “chefs” ready and willing to make protein based off of their instructions
- regulation: RNA is really really similar to DNA (which is why our cells can use DNA as a template for making those RNA copies) - but RNA is less stable - so it’s easier to degrade when you’re done with it, so you can shut down protein production when your cells have had enough (we looked at some of the mechanisms by which they do this yesterday: bit.ly/mrnalife
- alternative splicing: genes, the DNA versions of protein recipes, contain the instructions for what amino acids (protein letters) to link up in what order to make the protein of interest (in a process called translation) - but they also contain additional information. The “put this amino acid then that amino acid” parts of the genes are called exons because they are EXpressed. But in between these exons are stretches of DNA that contain regulatory information that’s important for transcription (DNA to RNA copying) and other nuclear stuff but these INterupting introns would just confuse the ribosomes because they don’t contain amino-acid-adding instructions and the ribosome can’t tell, so if it were to translate these interrupting Introns, the proteins would be gibberish. To prevent production of gibberish proteins, those introns are cut out during the mRNA-making process called SPLICING. And this splicing can be done in alternative ways to give you different “versions” of the same recipe. It’s like being able to make a chocolate chip cookie from a chocolate chip and walnut cookie recipe. Even though you have to do that splicing, and it may seem like you’re wasting a lot of DNA, you’re actually saving DNA because you don’t have to have 2 almost identical genes. But speaking of almost identical genes, another benefit of the exon/intron setup is…
- exon shuffling: sometimes, in the course of evolution, a gene gets duplicated. This is a key evolutionary “technique” because you now have a “backup copy” for natural selection to play with without having to worry about messing up the other version (note: I make it seem like evolution has a plan, but it doesn’t - it’s all just random - random mutations get made, and if they’re harmful they get selected against, if they’re neutral nothing changes, and if they’re beneficial they get selected for). As if that weren’t cool enough, sometimes exons from different genes can get joined to give you new proteins. Like taking the frosting instructions from a cake recipe and sticking them on your cookie recipe to get a frosted cookie.
By now, I’ve hopefully convinced you that this whole setup of DNA with extra regulatory info (introns) → mRNA copies with introns removed to leave only exons (and maybe not all of them) → “custom” proteins is cool and worth it. So now let’s go a bit more in depth. Because I’m the bumbling biochemist, and that’s what I do…
note: some of the rest of this will be a repeat of what I just said because most of the rest of this is a repost of a post I posted
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Негізгі бет Ғылым және технология Alternative splicing
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