Supersecondary Structure Code for RNA: Trace of Conformational Change on the Mycoplasma pneumoniae Ribosome and the R‑Loop Formation of Cas9

The shape of motifs is important for RNA functions and
deeply reflects
the structure of RNA at the supersecondary level, an intermediate
level between secondary and spatial structure. However, there is currently
no standardized classification system for the RNA supersecondary structures.
Primary and secondary occupied conformations, accounting for 73% of
the nucleic acid backbone units, were found by extending the concept
of protein supersecondary structure code (SSSC) combined with the
conformational code for organic molecules. The supersecondary structure
code for RNA (SSCR) was introduced as a conformational term for each
unit of the nucleic acid backbone using the letters P, S, T, and D,
denoting respectively the primary occupied conformation (P), the secondary
occupied conformation (S), the set of other conformations (T), and
disordered residues (D). The alignment of SSCR sequences was used
to compare with the different nucleic acid base sequences, depending
on the species. SSCR can also trace the conformational change of motifs
in RNA molecules such as ribosomal RNA (rRNA) and single-molecule
guide RNA (sgRNA) in the R-loop formation process of Cas9. The assignment
of supersecondary structure code T using the fuzzy search technique
of structural code homology is an effective and quick detection method
for motifs with conformational wobbling, such as the relatively rigid
TTT motifs of sgRNA with Cas9, streptomycin-binding RNA aptamer, 23S
rRNA, 2′-dG-II riboswitch, and human hepatitis B virus ε
pregenomic RNA, which work as the scaffold for protein and RNA molecules
or as the support stand for small external substrates.