UNCG tetraloop

A UNCG tetraloop is an RNA tetraloop whose four loop positions follow U–N–C–G, where N can be any ordinary RNA nucleotide. The pattern permits UACG, UCCG, UGCG and UUCG. It specifies the loop sequence family; the closing stem pair lies outside these four positions.

For example, GGACUUCGGUCC can be represented with stem pairs1–12,2–11,3–10 and4–9, leaving UUCG at positions5–8. Four stem pairs and four loop nucleotides give twelve residues. The closing stem pair in this representation is C–G; it is not part of the UNCG sequence. This is sequence bookkeeping for the cited structural RNA, not a claim that every UNCG-containing sequence forms the same isolated hairpin.

A solution NMR spectroscopy study of that hairpin used interproton distances and scalar couplings to construct a restrained three-dimensional model. The reported loop includes an unusual G–U interaction and syn-oriented loop guanosine; mutations of conserved loop residues reduced stability.^[ref] Thus a four-residue loop in a secondary-structure description can still contain specific internal contacts, including a noncanonical base pair. It is not four freely moving bases attached to a stem.

A useful experimental comparison changes loop sequence while preserving a stated stem and solution conditions. RNA optical melting asks how the transition changes; NMR asks which spatial contacts are compatible with its measurements. These tests address related but different questions. Similar melting midpoints do not independently establish identical loop geometry, and one sequence motif does not establish its fold in every larger RNA.

The conserved letters help identify candidates for a structural family. The choice at N, neighboring stem, chemical modifications and surrounding RNA remain part of the molecular specification.