Multiloops

In RNA secondary structure, a multiloop (also called a multi-branch loop or junction) is a region where three or more helices terminate and connect through a loop of unpaired nucleotides. It contrasts with hairpin loops formed by a single helix, and with bulges or internal loops that involve two adjacent helices. Multiloops occur in RNAs with complex folds and can be essential for bringing distant regions into proximity.

Multiloops are defined by the number of branches that meet in the loop and by the number of unpaired nucleotides within the loop. Their size and topology influence RNA flexibility and function, and they are common in large or structurally intricate RNAs such as ribosomal RNA and various long noncoding RNAs. The arrangement of branches around a multiloop can affect how the RNA interacts with proteins and other molecules.

In computational RNA structure prediction, multiloops are treated as distinct structural elements with specific energy penalties in thermodynamic models. Prediction programs such as Mfold and ViennaRNA assign a cost for opening a multiloop, plus contributions for loop size and the number of branches, influencing the minimum-energy structure that is predicted. Dot-bracket notation can represent multiloops as unpaired regions flanked by multiple base-paired segments, highlighting their role as junctions in the overall fold.

Biologically, multiloops provide adaptable junctions that accommodate binding sites and structural rearrangements. Their presence can complicate experimental structure probing and computational prediction due to the combinatorial possibilities they introduce in RNA folding.

See also: RNA secondary structure, hairpin loop, internal loop, bulge, junction.