FIGURE 2.

Examples of cis and trans interactions during cotranscriptional folding. (A) Hypothetical RNA sequence, capable of forming helices h₁–h₄, at sites A–E. (B) Transcription of the sequence across time points t₁–t₅, with the sequential lengthening of the 3′ end. The transcription process limits the available sites for helix formation, imposing an order on helix formation. If an early-formed helix is stable, it can serve to block the formation of subsequent helices by occupying specific sites. (C) Sites may also be occupied due to interactions with other molecules; in this case, a protein-binding site (PBS) occupies site A, leading to a very different result. (D) If early helices are relatively unstable, they can be seen as transient helices that yield to new helices. This mechanism can aid the robust formation of desired structure features. Note that some of the conformations shown above correspond to the ones introduced and defined by Meyer and Miklós (2004). These are as follows: In B, h₁ (iī) and h₃ (ic) are 3′-trans, where h₁ is stable, preventing the formation of h₃, and h₁ (īi) and h₂ (ic) are 3′-cis, where h₁ is stable, preventing the formation of h₂; in D, h₁ (ci) and h₂ (iī) are 5′-cis, where h₁ is an intermediate for h₂, and h₂ (ci) and h₃ (iī) are 5′-cis, where h₂ is an intermediate for h₃.