Nucleic Acids!!!!! All the awesome stuff I study – everything from DNA to proteins – and even the bench I work at – it’s all made up of ATOMS which we talked about a couple weeks ago: http://bit.ly/2wvkWWv

When atoms come together, complex molecules can be formed. Things like DNA and proteins. Instead of building these big macromolecules from scratch each time, your cells stock up on “building blocks”. Last week we looked at the building blocks of proteins, amino acids. http://bit.ly/2KBFRiS 

The instructions for what order to put those amino acid building blocks together are written in the genetic language of nucleic acids (DNA & RNA), which has a different alphabet. Today let’s look at the building blocks of nucleic acids (RNA(RiboNucleic Acid) & DNA(DeoxyRiboNucleic Acid)) – nucleotides 

Similarly to the amino acid protein letters, nucleotide DNA/RNA letters have generic backbones for easy linking (a sugar-phosphate backbone for nucleic acids and a (carboxylic acid-alpha carbon -amino group) for amino acids, but they also have unique parts that give them different properties. 

For nucleotides, the unique parts are nitrogenous bases and they can form specific base pairs with each other (A to T (or U in RNA)) and C to G. This way you can use one strand of double-stranded DNA as a template for making the other one. 

For amino acids, the unique parts are the “side chains” or “R groups” which range from small and flexible to large and bulky, negative, positive, or neutral. These different properties help proteins fold up into intricate shapes and carry out various functions. But in order to get those functional proteins you have to make sure you link up the write letters and this is one where DNA comes in.

The instructions for what order to link the amino acids in are written in DNA as genes. Because those instructions are so important, this DNA is kept “locked up” safe and sound in a membrane-bound “room” in your cells called the nucleus. It’s kinda like a “reference section” of a library – you can’t check out books, but you can read them & even make copies. 

If you need to make a protein, you have to find the recipe for it 🕵️‍♀️ Then you have to TRANSCRIBE a copy of it into the related RNA language ✍️ ⏩ Then you can take this MESSENGER RNA (mRNA) copy out of the nucleus & into the CYTOPLASM (general cellular interior) where RIBOSOMES (protein/RNA molecular machines) TRANSLATE the mRNA into the PROTEIN language of AMINO ACIDS 👩‍🍳

The combination of ALL the DNA in one of your cells is called your GENOME 👍 You can think of it like a super long cookbook where the recipes for making proteins, functional RNAs, etc. are regions of DNA called GENES 👍

The genome’s split up into “volumes” 📚 called CHROMOSOMES 👉 you have 46 of them. 46? 🤨Then why’s it called “23 and me?” 🤷‍♀️ 23 *pairs* 👉 you have 2 copies of each volume 👉 1 you inherited from each of your biological parents. 

The copies are mostly the same (except for the pair of sex chromosomes which can be different) 👉 they have recipes for making the same things BUT small differences in the recipes (POLYMORPHISMS) lead to slight differences in the final products &/or when they’re made 👉 This variety is good 👍 (polymorphisms are the spice of genetic life 🤓) BUT you might also have “typos” (harmful mutations) in 1 copy of a recipe, but thankfully you have a backup! 😅 (🤞 your backup’s ok)

Just like proteins have layers of structure (primary structure’s sequence of amino acids, secondary structure’s things like helices & strands made through backbone-backbone interactions, tertiary involves side chains, & quaternary involves more than one polypeptide chain) nucleic acids have structure too. The sequence of nucleotide “letters” in nucleic acids (DNA & RNA) defines its PRIMARY STRUCTURE & base-pairing between those nucleotides gives it SECONDARY STRUCTURE 

And just like with proteins, the primary structure is of primary importance, so let’s take a closer look at these nucleic acid letters!

POLYMERS are chains of similar units (MONOMERS) ⛓ 👉 NUCLEIC ACIDS are POLYMERS made up of NUCLEOTIDE MONOMERS 👍

These MONOMERS 👆 are themselves made up of key components 👉 NUCLEOTIDES contain 👇

  • a NITROGENOUS (nitrogen-containing) BASE (aka NUCLEOBASE)
  • a PENTOSE (5-carbon SUGAR) 👉 either ribose (in RNA) or deoxyribose (in DNA)
  • 1 or more PHOSPHATES (➖ charged) ⚡️

building nucleic acids up from their parts 👇

  • BASE 
  • BASE + SUGAR = nucleoSIDE
  • BASE + SUGAR + PHOSPHATE = nucleoTIDE 
  • NUCLEOTIDE + NUCLEOTIDE + NUCLEOTIDE . . . = NUCLEIC ACID
  • NITROGENOUS BASES (NUCLEOBASES) 👉 5 common ones; 3 are found in both RNA & DNA 👉 adenine (A), guanine (G), & cytosine (C); thymine (T) is only found in DNA & uracil (U) is only found in RNA

👆 bases can be classified as purines (A & G) & pyrimidines (C, T, U) 👉 remember PURe As Gold 🏆

purines have 2 rings (1 6-membered, 1 5-membered) (I remember this by thinking of purines as “pure” – having it all) as opposed to pyrimidines which only have 1 ring (6-membered) 👍

NUCLEOSIDES 👉 when 👆 bases hook up to a Sugar (through a GLYCOSIDIC BOND) they become nucleoSides 👉 ribonucleosides if they bind to ribose & deoxyribonucleosides if they bind to deoxyribose (like ribose but w/1 less oxygen) 👍

NUCLEOTIDES 👉 when nucleoSides hook up with phosphate groups they become nucleoTides 👇

  • +1 phosphate 👉 nucleoside MONOphosphate (NMP (if the nucleoside has ribose as the sugar) or dNMP (if the sugar’s deoxyribose))
  • +2 phosphates 👉 nucleoside Diphosphate (NDP or dNDP)
  • +3 phosphates 👉 nucleoside TRIphosphate (NTP or dNTP)

📝 it may 👀 confusing that the nucleoTides have nucleoSide in their name as ✍️ above, but that’s because it’s ✍️ as its parts 👉 nucleoSide + phosphate (nucleoTide has the phosphate so if we ✍️ nucleoTide monophosphate, etc. that would be “redundant”

These “weddings” 💒 also come with name changes 👇

  • purines 👉 end in “-sine”
  • pyrimiDines -> end in “-Dine”

Nucleotides join together through PHOSPHODIESTER LINKAGES to form NUCLEIC ACIDS 👇

🔹 covalent backbone of nucleic acids consists of alternating phosphate & pentose residues w/nitrogenous bases as “side groups” joined to backbone @ regular intervals 👍

But how best to accommodate it all? The sugar-phosphate backbone is ➖ charged & HYDROPHILIC (water-loving) but nucleobases are HYDROPHOBIC (water-avoiding) 👉 nucleic acids try to form secondary structures that minimize exposure of bases to water & maximize exposure of the backbone to water 👍

DNA usually does this through forming a DOUBLE HELIX made up of 2 DNA strands running in opposite directions (ANTIPARALLEL) 👉 double-stranded DNA (dsDNA)

In the helix, bases pair in the center like rungs in a ladder – the bases are planar (flat), so their rings “stack” like pancakes 🥞 👉 “glue” strands together 👍

The width of the helix is constant bc 1 PURINE (2-ringed base) & a PYRIMIDINE (1-ringed base) always join together 👉 C to G & A to T

To accommodate this pairing, the strands adopt a right-handed helical form (to see that it’s right handed, give a thumbs up w/right 🖐 (the OPPOSITE of the Apple 👍) 👉 direction your fingers are curling is direction DNA curls)

The most common double helix in DNA is “B-form” It has 2 grooves – a larger major groove, & narrower minor groove 👉 can act like windows for other molecules to “read” their sequence. RNA can also form double helixes (though usually a more compact “A-form”) & it also forms a variety of structures w/in single strands 

But that’s not where the structure stops! – your DNA packs up tight w/help of HISTONES because we have so much DNA it’d never fit in our cells if it weren’t all coiled up (if you stretched it out it would be ~2m (~6.5ft) long 🤯) To help it coil & stay coiled ➿ it wraps around “hair rollers” (proteins called HISTONES) to form NUCLEOSOMES, which are like beads on string ➰

👆saves space (& prevents things you don’t want read from being read), but when you *do* want a region read &/or transcribed, that region must be “opened up” 👉 It’s kinda like when you open a mobile version of a website 📱 & it has all the different sections collapsed to save room ▶️ & you have to click on them to expand them if you want to actually read them 🔽

Much of EPIGENETICS involves special proteins adding modifications to the DNA or its “curlers” that help the sections expand if you want to read them 🔽 & collapse if you don’t want them read 🔼

How do you know what’s worth reading when? 🤷‍♀️ Other proteins are able to read section headers 👉 recognize specific DNA sequence motifs (like words) 👍 Instead of reading gene-specific headers, it’s more like reading “key words” or indexing terms 👉 so a DNA-binding protein can search for 1 search term & get “hits” on multiple regions or genes which it can act on “simultaneously” 👉 allows for coordinated activation or deactivation of related genes 👍

More on topics mentioned (& others) #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0 

Thanks again to the IUBMB for helping share this message as student ambassador- be sure to follow them for great biochemistry from around the world. 

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