10.4: RNA Structure

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We have learned about different functions of RNA, and it should be clear by now how fundamental the role of RNA in living systems is. Because it is impossible to understand how RNA actually does all these activities in the cell, without knowing what its structure is, in this part we will look into the structure of RNA.

RNA structure can be studied in three different levels:

Primary structure: the sequence in which the bases (U, A, C, G) are aligned.
Secondary structure: the 2-D analysis of the [hydrogen] bonds between different parts of RNA. In other words, where RNA becomes double-stranded, where RNA forms a hairpin or a loop or other similar forms.
Tertiary structure: the complete 3-D structure of RNA, i.e. how the string bends, where it twists and such.

As mentioned before, the presence of ribose in RNA enables it to fold and create double-helixes with itself. The primary structure is fairly easy to obtain through sequencing the RNA. We are mainly interested in understanding the secondary structure for RNA: where the loops and hydrogen bonds form and create the functional attributes of RNA. Ideally, we would like to study the tertiary structure because this is the final state of the RNA, and what gives it its true functionality. However, the tertiary structure is very hard to compute and beyond the scope of this lecture.

Even though studying the secondary structure can be tricky, there are some simple ideas that work quite well in predicting it. Unlike proteins, in RNA, most of the stabilizing]free energy for the molecule comes from its secondary structure (rather than tertiary in case of proteins). RNAs initially fold into their secondary structure and then form their tertiary structure, and therefore there are very interesting facts that we can learn about a certain RNA molecule by just knowing its secondary structure.

Finally, another great property of the secondary structure is that it is usually well conserved in evolution, which helps us improve the secondary structure predictions and also to find ncRNA (non-coding RNA)s. There are widely used representations for the secondary structure of RNA:

Figure 10.1: Graphical representation of the hierarchy of RNA strucure complexity © Stefan Washietl. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Figure 10.2: The typical representation of RNA secondary structure in textbooks. It clearly shows the secondary substructure in RNA. © Stefan Washietl. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Figure 10.3: Graph drawing where the back-bone is a circle and the base pairings are the arcs within the circle. Note that the graph is outer-planar, meaning the arcs do not cross. © Stefan Washietl. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Formally: A secondary structure is a vertex labeled graph on n vertices with an adjacency matrix A = (aij) fulfilling:

• a_i,i+1 = 1for1 ≤ i ≤ n1 (continuous backbone)
• For each i, 1≤i≤N there is at most one a_ij =1 where \(j \gneqq i+/-1\)(a base only forms a pair with one other at the time)
• If a_ij =a_kl =1andi<k<jtheni<l<j (ignore pseudo knots)

Figure 10.5: A matrix representation, in which you have a dot for each pair. © Stefan Washietl. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Figure 10.6: Mountain plot, in which for pairs you go one step up in the plot and if not you go one step to the right. © Stefan Washietl. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.