The unknotted strands of life: knots are very rare in RNA structures

TL;DR

This study systematically screened around 6,000 RNA structures and found that knots are extremely rare, indicating that RNA folding mechanisms likely minimize entanglement more effectively than other biopolymers.

Contribution

It is the first large-scale systematic screening of RNA structures for knots, revealing their scarcity and suggesting specialized folding mechanisms.

Findings

Only three deeply-knotted RNA molecules identified

RNA knots are much rarer than in proteins and viral DNA

RNA folding may be evolutionarily optimized to prevent entanglement

Abstract

The ongoing effort to detect and characterize physical entanglement in biopolymers has so far established that knots are present in many globular proteins and also abound in viral DNA packaged inside bacteriophages. RNA molecules, on the other hand, have not yet been systematically screened for the occurrence of physical knots. We have accordingly undertaken the systematic profiling of the ~6,000 RNA structures present in the protein data bank. The search identified no more than three deeply-knotted RNA molecules. These are ribosomal RNAs solved by cryo-em and consist of about 3,000 nucleotides. Compared to the case of proteins and viral DNA, the observed incidence of RNA knots is therefore practically negligible. This suggests that either evolutionary selection, or thermodynamic and kinetic folding mechanisms act towards minimizing the entanglement of RNA to an extent that is unparalleled by other types of biomolecules. The properties of the three observed RNA knotting patterns provide valuable clues for designing RNA sequences capable of self-tying in a twist-knot fold.