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mRNA splicing and alternative splicing - the good, the bad, and the bakery 3 года назад


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mRNA splicing and alternative splicing - the good, the bad, and the bakery

The “original recipes” for proteins are called genes, and they’re written in DNA. A bunch of genes are hooked up back-to-back with some “spacer content” in “cookbook volumes” called chromosomes. Humans have 23 chromosomes & we get 1 copy of each from each parent (22 of them at least are mostly identical except for slight different variations in the genes (allelic variation) that give us diversity - the 23rd chromosome (the “sex chromosome”) has an x & a y version which are more different from one another, and you get one of those (x or y) from each parent.⠀ blog form with graphics & rest of text: https://bit.ly/mRNAsplicing note: text is a short version of a longer more detailed post from January you can find on my blog here: https://bit.ly/altsplicing ⠀ Your whole collection of chromosomes is called your genome and in our cells (and the cells of other eukaryotes (basically most things that aren’t bacteria) it’s housed in a membrane-bound compartment of the cell called the nucleus (don’t confuse this with the atomic nucleus, which is the central hub of atoms where protons hang out).⠀ ⠀ Instead of telling you to add vanilla & sugar, genetic recipes tell you to add valine (V) & serine (S) & (as well as 18 other amino acids that serve as protein “building blocks”) to make chains of amino acids that fold up into proteins. The recipes specify how much of each & in what order to add them & this “baking” process is called translation.⠀ ⠀ The nucleus serves as a kind of “reference section” of the cellular library -  it has a ton of important info, but you can’t “check it out” from the nucleus. Instead, if you want to use it, you have to make a copy (a process called transcription) & take it out of the nucleus into the “kitchen” of the cytoplasm (the main interior part of the cell) where the “chefs” (ribosomes) are⠀ ⠀ The copy machine (RNA polymerase) is in the nucleus & makes a copy of gene in RNA (RiboNucleic Acid) instead of DNA. RNA’s really similar to DNA & holds the same “info” but it’s less stable so it’s kinda like making a copy w/a shorter-lasting ink. First, RNA pol copies the gene “word for word” to make pre-messenger RNA (pre-mRNA). But this pre-mRNA copy has more info than the chefs need.⠀ ⠀ In addition to telling you what to add where (what the chefs need), genetic recipes contain “margin notes” (introns)  providing info about things like when to make copies & “suggested pairings” (if you’re making this you might also want to make…). These notes are regulatory information & they’re important, but they’re “upstream” of the chefs who are just following orders from upper management. The chefs don’t need this info, so it gets cut out of the recipe copy before it’s given to them. The process of RNA splicing cuts out the regulatory info to turn pre-mRNA into mature mRNA. ⠀ ⠀ Those “margin notes” getting cut out are called introns because they INTerrupt the EXpressed “add this” steps (called EXONS) & provide unique opportunities for making variations of the same basic recipe.⠀ ⠀ Say you have a recipe for a 3-layer cake with a layer of chocolate cake 🍫, then a layer of strawberry cake 🍓, topped off with a layer of vanilla cake 🍨 (🍫🍓🍨). If you split up the “make chocolate layer,” “make strawberry layer” & “make vanilla layer” steps you can cut 1 or 2 out of the recipe before handing it to the chef. So the same basic recipe can be altered to make a chocolate/strawberry cake 🍫🍓, a chocolate/vanilla cake 🍫🍓, a strawberry/vanilla cake 🍓🍨, a chocolate cake 🍫, a strawberry cake 🍓, or a vanilla cake 🍨!⠀ ⠀ Introns allow you to mix n’ match to make different proteins from the same instructions. This decreases the amount of DNA we need which is good because (although we don’t have as much as the lungfish) we already have a TON of it - so much so that we have to wind & wind & wind it up to get it to fit inside the nucleus. ⠀ ⠀ The alternative splicing only changes the RNA copy - NOT the gene itself -so you don’t have to worry about messing up your original recipe, but your options are limited. BUT if a gene gets duplicated so you have 2 copies of the recipe in your cookbook, evolution can play around w/the 2nd copy & make permanent changes in the GENE itself without messing up the 1st. So you can do things like duplicate 1 of the exons (get a 2nd chocolate layer 🍫🍫🍓🍨) or even mix n’ match with other genes (maybe add a layer of frosting by adding on an exon from a different gene). We call this exon shuffling & it can lead to genes with new functions.⠀ ⠀ It’s important to remember that all of those changes happen RANDOMLY - evolution doesn’t have a motive, but changes will “only” stick around if they’re useful (or at least not harmful on balance) - most genetic changes will be neutral or harmful but changes that are harmful will lead to lower survival - thus natural selection will “weed them out”⠀

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