  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.
