RNA tetraloop (source code)

= RNA tetraloop
{c}

An \b[RNA tetraloop] is the four-nucleotide loop capping the paired stem of an <RNA hairpin>. The four count excludes the two <nucleotides> of the closing <base pair>. A tetraloop is therefore a local <RNA secondary structure> motif, not necessarily an entire four-nucleotide <RNA> molecule.

For an original sequence illustration, `5'-GGCGAAAGCC-3'` can be drawn with pairs 1–10, 2–9 and 3–8. The central `GAAA` at positions 4–7 forms a four-residue loop; three stem pairs plus four loop residues give $2(3)+4=10$ <nucleotides>. Whether a particular sequence actually favors that conformation requires experimental or structural evidence.

Comparative analysis of <ribosomal RNA> identified recurrent motif families, including <GNRA tetraloops> and <UNCG tetraloops>, as well as the less common CUUG motif. The study also found relationships between loop sequence and its closing pair.<Architecture of ribosomal RNA: constraints on the sequence of "tetra-loops" by Carl R. Woese and others>[Abstract, recurring motifs and closing-base-pair preferences.]{ref} In GNRA, N means any of the four ordinary <RNA> bases and R means a <purine>, A or G; GAAA is one example. UUCG belongs to UNCG, with its N position occupied by U.

A simple sequence count separates a motif pattern from a frequency claim. Four unrestricted positions give $4^4=256$ possible sequences. GNRA specifies the first and last bases and permits $4\times2=8$ sequences; UNCG permits 4. These counts assume the usual A, C, G, U alphabet. They do not say that the sequences occur equally often or have identical stability.

The stem and loop environment matter together. Optical-melting measurements on 24 selected stem–loops quantified sequence-dependent thermodynamics rather than treating every four-residue loop as one energetic object.<Thermodynamic characterization of naturally occurring RNA tetraloops by Justin P. Sheehy and others>[Abstract and sequence-design/thermodynamic-analysis sections.]{ref} A frequently observed motif and a particularly stable isolated hairpin are different scientific observations; both can inform how <RNA> structures are understood.