RNA and Riboswitches

"In the beginning, RNA was a simple molecule, but over time it has gained many functions. From self-replication, to storing and utilising information, to regulating cellular pathways, it is an example to all molecules..."

The Central Dogma

The central dogma is used to explain how information encoded on DNA is used to create what we know as life. Essentially, DNA is converted to RNA which is converted to proteins (figure 1).

DNA (Deoxyribonucleic acid) is a polymer molecule (made up of sub-units called nucleotides or bases) which has a double stranded helical structure (figure 1a). There are four types of bases (Guanine - G, Cytosine - C, Adenosine - A, and Tyrosine - T)which can be joined together in many different conformations to form different DNA molecules, and each type of base is able to pair with one other type; C pairs with G, and A pairs with T (figure 2). Bases which pair are described as being complementary.
DNA's primary job is to store biological information in the form of genes, which are encoded by the bases which make up the DNA molecule. For example, CGGGATGTATTAC could encode for a specific gene.

RNA (RiboNucleic Acid) is similar to DNA in that it is a polymer molecule and made up of nucleotides/bases, but it differs in a few crucial ways. The first is that usually RNA is made up of only a single strand, as opposed to DNA's double stranded structure (figure 1b). The second is that in RNA, the Tyrosine (T) base is not used, instead it is replaced with Uracil (U).

As mentioned above, RNA is the second stage of The Central Dogma. Usually, a type of RNA termed mRNA is used as an intermediate between DNA and proteins and is made using DNA as a template, meaning that the sequence of the RNA molecule is determined by the sequence of the DNA from which it is copied. There are many reasons why an intermediate is required instead of simply using DNA. These reasons include:

• Protection of the DNA: damage to DNA can cause unfavourable mutations so it is safer to use a 'copy' rather than the original,
• Regulatory reasons: the presence or absence of RNA can correspond to the presence/absence of the protein which it encodes for, meaning that it can be used to control cellular pathways
• Inability of DNA to reach protein machinery: in eukaryotic cells (animals, plants, fungi, etc.), the DNA is separated from the rest of the cell by a nuclear envelope, DNA is unable to pass through this envelope but RNA is able to

Proteins are the end product of The Central Dogma and are used to carry out functions and generally create what we recognise as life. Proteins are also polymer molecules made up of subunits, but unlike with DNA and RNA these subunits are not bases/nucleotides, they are amino acids. Amino acids are relatively simple molecules which all share a generic structure, but have different functional (R) groups (figure 3). The interactions of the functional groups, both with other functional groups of the same/different proteins, and with other molecules/etc. in its environment, gives the protein its overall function. These functions can range from catalytic (speed up the rate of a reaction) to structural (shape/strength of a cell), to virulence (causing disease in a host).

As can hopefully be seen from above, RNA is a vital part of The Central Dogma, and therefore is fundamental to life.

The RNA Molecule

As has been mentioned briefly, RNA is a single stranded, helically structured polymer molecule made up of nucleotides/bases. While it may seem that this structure is much simpler than DNA, the fact that it doesn't have all of its bases already paired to its complementary strand means that the RNA's nucleotides are free to base pair in many different ways. For example, the RNA molecule could base pair with itself (figure 1a) or other molecules to form a complex (figure 1b). The ways in which the RNA bases interact defines the (secondary) structure of the molecule, so therefore the sequence of the RNA molecule defines the structure of the molecule. This means that if a specific RNA structure is required, then it should be able to be achieved by giving the RNA a specific sequence. This is shown in figure 2. The RNA molecule has two sections which are complementary to each other, which can therefore base pair to create a stem region. The bases which are not complementary remain un-paired and create a loop at the top of the stem section. The fact that RNA is able to fold into many types of secondary structures means that it can have a variety of functions.

One cellular process in which RNA is heavily involved is that of protein synthesis. We have already mentioned how RNA acts as an intermediate and contains a sequence which corresponds to the amino acid sequence of a protein, but we haven't mentioned how this happens.

mRNA (messenger RNA) is able to encode for amino acids through the use of 'triplets', also known as 'codons'. These are simply three bases on mRNA which corresponds to a single amino acid, of which there are 21 (natural) types (figure 2). For example, the codon AUG codes for the amino acid methionine (M).

While codons allow mRNA to encode the amino acid sequence of a protein, they do not explain how this information is used practically. In order to do this, we must look at another type of RNA; tRNA (transfer RNA). AS can be seen in figure 3, tRNA has an interesting secondary structure, and two important regions. The first of these regions is the attachment site at the top of the tRNA, which is where a specific amino acid to the tRNA is able to attach. The second region is the anti-codon at the bottom of the molecule. The anti-codon is complementary to the codon for the amino acid which is attached to that tRNA, allowing the tRNA to bind to the mRNA, and hence ensure that the amino acid is added to the sequence in the correct place (figure 4).

There is still one more main part of this mechanism which is missing, and that is how the amide bonds between amino acids are formed in order to synthesis the protein. Once again, RNA comes to the rescue, this time in the form of rRNA (ribosomal RNA). The are different types of rRNA, and they come together (along with some proteins) to form a specific complex called a ribosome (figure 5, also pictured in our logo). The ribosome's job is to bind to the mRNA and 'read' along it, ensuring that the correct tRNAs are added at the right time (figure 6).

Protein synthesis is just one of the many pathways and processes in which RNA is involved, in the next section we will see how RNA can help regulate cellular pathways.