Nucleic Acids, A Primer

Haha! I’m so funny! You know, because nucleic acids make up DNA and RNA, and DNA replication requires an RNA primer, and I’m losing my mind because help me…

I’m kidding. This stuff is fun. Just, you know, in smaller doses, and not at ten o’clock at night. Oh well, it can’t be helped. Right? Right.


Nucleic acids are pretty much literally the basis of life as we know it. (Not in the actual literal sense. Yes, I took Orgo, I know how important carbon is. I write SciFi—I understand how useful that second-row tetravalent element is. I’m just trying to be poetic. Roll with me here.) DNA encodes all of our characteristics, and RNA translates that code into proteins (using a very interesting process that involves rRNA using tRNA to make proteins from a code in mRNA….). We use nucleotide triphosphates for energy literally all the time. Don’t even get me started on ATP…

All of that being said, they’re actually astoundingly simple little buggers. Even with all of the complexity, all of the beautiful variety of sequences and functions, all of nucleic acid chemistry can be boiled down to five modest little bases.

bases

The three innocent little pyrimidines on the left and the two friendly purines on the right make up all nucleic acids as we know them. (Well, almost all of them. Don’t make me drag those modified ones into this, please.) Their relationships with each other have been drilled into us since we were born: adenine bonds to thymine (DNA) or uracil (RNA), guanine bonds to cytosine.

However, this is just the first step. To really get anywhere interesting, we have to link our bases to sugars. This step, in which we either bond a base to ribose (RNA) or 2′-deoxyribose (DNA), produces nucleosides. My fave, thymidine, is pictured below for reference.

thymidine

“Hi! I helped one of June’s characters show off in a SciFi story!”

As you can see in the picture above, the base binds on the same side as that dangly “CH2OH” group. That makes the bond that connects it to the sugar a beta-N-glycosidic bond. That’s how all nitrogenous bases bind to their sugars.

Okay, so we’ve taken thymine (a base) and added deoxyribose to make thymidine (a nucleoside). We all know that DNA and RNA are made up of nucleotides. What’s the distinction?

Well, a nucleotide is produced when you string phosphates onto that OH group (the 5′-OH) dangling off to the side. If you were to string a single phosphate group onto my thymidine above, what would you make? Thymidine 5′-monophosphate, or 5′-TMP, or just TMP. (If, say, you were to string three phosphates onto an adenosine, you’d make ATP.) Sometimes, the phosphate group will bond to both the 5′- and the 3′-OH group on the sugar, making, for example, cyclic-AMP, or cAMP.

Now, as you’ve already deduced (or been told multiple multiple times in my posts on ATP), adding multiple phosphates introduces multiple high-energy bonds that can be cashed in for energy when the cell needs to synthesize things. However, NTPs serve another important purpose: they make up nucleic acids.

Nucleic acids are strings of nucleotides that result from successively attaching the 5′-phosphate of a nucleotide to the 3′-OH of the one before it. When you do this with nucleotides made of ribose, you get RNA; if you do it with deoxyribose, you get DNA.

Because one end of the strand has a free 5′-phosphate and the other has a free 3′-OH, DNA and RNA are said to have a directionality about them. Typically, we consider the 5′ end to be the “beginning” (when we’re talking about sequences and polymerization) and the 3′ end to be the “end.”

As we know, DNA and RNA are characterized mostly by the sequence of their bases. (In other words, as far as information content is considered, the phosphates and the sugars mean squat.) We also know that DNA is the carrier of genetic information (occurring in extremely long strands in every cell), while RNA is a general workhorse for cellular processes (occurring in about eight times the abundance of DNA).

Now, DNA mostly just sits around and looks pretty, getting pampered by enzymes that protect it and repair it (the only molecule that our body actually deems important enough to repair instead of scrapping altogether). Meanwhile, RNA runs itself ragged, making proteins (rRNA), carrying around amino acids (tRNA), shuttling information from DNA (mRNA), splicing transcripts (snRNPs)… you get the idea.

As much as it seems unfair to push all the work off on RNA, DNA actually has a pretty important job on its own. However, the structure and function of the molecule didn’t just fall in our lap one day. It required a bit of work to figure out.

First, Chargraff analyzed the relative amounts of the four bases in DNA in a lot of different organisms. What he found won’t come as a surprise now, but it was pretty important back then—while A, T, G, and C aren’t all present in equal amounts, the amount of A equals the amount of T, and the amount of G equals the amount of C. In other words, the amount of purine in DNA equals the amount of pyrimidine.

After that, Watson and Crick used this information, along with data from X-ray diffraction, to figure out that DNA consisted of a complementary double helix with specific base pairs. What this means is that DNA is composed of two strands that wind around each other, held together by very specific hydrogen-bonding interactions between pairs of bases (A:T, C:G).

This may not seem like earth-shattering information now, but its meaning is really quite profound: DNA is a four-digit code, and other molecules in the cell (tRNA) translate this code into the language of amino acids. A specific triplet (“codon”) of bases codes for a specific kind of amino acid, and specific sequences of amino acids fold up to make molecules of wonky and complex shapes, functional shapes that we usually call “proteins.”

However, let’s not forget about RNA. Although it’s usually single-stranded and doesn’t contain genetic information (unless you’re an RNA virus), it does a lot of different things, from carrying and interpreting DNA’s code to actually being a freaking enzyme.

mRNA, or “messenger RNA,” is the way that DNA’s code is translated into protein. Made in a process called “transcription,” it carries specific pieces of genetic information (genes) to ribosomes, which can translate them into proteins. Oh, yeah, while we’re at it, we might as well mention that the other parts of that process completely depend on RNA—ribosomes are made of enzymatic RNA (rRNA), and they use tRNA (transfer RNA) to translate the genetic code into an amino acid sequence. Tiny pieces of RNA, called small nuclear RNAs, associate with proteins to form snRNPs, which help splice transcripts. siRNAs silence gene expression. Other RNAs have other regulatory roles.

Now, before we dive off the deep end and take on nucleic acid structures head-on, let’s back up and talk about a main distinction between DNA and RNA. Functionally, they’re extremely diverse, one cloistered and compartmentalized (if you’re eukaryotic), the other overworked and oftentimes promiscuous. However, it’s worth noting that, while RNA is susceptible to hydrolysis by base, DNA is not.

The reason for this is simple: the mechanism for hydrolysis in base involves the 2′-OH group that’s present in DNA. All a basic group has to do is pull a proton off of the 2′-OH, and it goes hunting for a phosphate group, which it finds in the bond that connects it to the next base in the sequence. When it attacks it, it forms a cyclic intermediate that involves both the 2′- and 3′-OH groups. This can be hydrolyzed to form either 2′- or 3′-phosphate products.

Phew! All right! You never knew there were so many tedious details to know about nucleic acids, amirite? Unfortunately, this is only the start—next, we’re going to talk about the conformational structures of DNA. I can see you’re practically jumping out of your seat.

(Me too, buddy.)


I’m going to retrieve a Snicker’s bar and a flavored water. Anyone want anything…?

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