Pseudoknots

A pseudoknot is a feature of RNA secondary structure in which bases in a loop pair with a sequence outside that loop, creating a crossing interaction when the structure is drawn as a two-dimensional map. This non-nested pattern cannot be represented by simple, non-crossing base-pair models.

The most common form is the H-type pseudoknot, consisting of two stems (S1 and S2) connected by two loops (L1 and L2). In S1, a hairpin loop base-pairs with a complementary region downstream to form the second stem, producing a compact, knot-like topology. More complex pseudoknots can involve additional stems and loops.

Biological significance: Pseudoknots are widespread in nature. They serve structural and functional roles in many RNAs, including signals that induce programmed ribosomal frameshifting in viruses, and in telomerase RNA where the pseudoknot contributes to enzyme activity. They can stabilize three-dimensional folds, influence catalytic activity of ribozymes, and modulate translation or RNA processing.

Detection and study: Experimental approaches such as chemical probing, nuclear magnetic resonance, and X-ray crystallography can verify pseudoknots. Computational prediction is more challenging than for non-crossing structures; specialized algorithms and energy models are used to identify crossing base pairs, though predictions are less reliable than for nested structures and often require experimental confirmation.