Stem-loop intramolecular
base pairing is a pattern that can occur in single-stranded
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in
nucleotide sequence when read in opposite directions, base-pair to form a double helix that ends in an unpaired loop. The resulting structure is a key building block of many RNA
secondary structures. As an important secondary structure of RNA, it can direct RNA folding, protect structural stability for
messenger RNA (mRNA), provide recognition sites for RNA binding proteins, and serve as a substrate for enzymatic reactions.
Formation and stability
The formation of a stem-loop structure is dependent on the stability of the resulting helix and loop regions. The first prerequisite is the presence of a sequence that can fold back on itself to form a paired double helix. The stability of this helix is determined by its length, the number of mismatches or bulges it contains (a small number are tolerable, especially in a long helix) and the base composition of the paired region. Pairings between
guanine
Guanine () (symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is c ...
and
cytosine
Cytosine () (symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached ...
have three
hydrogen bonds and are more stable compared to
adenine-
uracil pairings, which have only two. In RNA, adenine-uracil pairings featuring two hydrogen bonds are equal to the adenine-
thymine bond of the DNA. Base stacking interactions, which align the
pi bond
In chemistry, pi bonds (π bonds) are covalent chemical bonds, in each of which two lobes of an orbital on one atom overlap with two lobes of an orbital on another atom, and in which this overlap occurs laterally. Each of these atomic orbita ...
s of the bases'
aromatic rings in a favorable orientation, also promote helix formation.
The stability of the loop also influences the formation of the stem-loop structure. "Loops" that are fewer than three bases long are
sterically
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
impossible and do not form. Large loops with no secondary structure of their own (such as
pseudoknot pairing) are also unstable. Optimal loop length tends to be about 4-8 bases long. One common loop with the sequence UUCG is known as the "
tetraloop
Tetraloops are a type of four-base hairpin loop motifs in RNA secondary structure that cap many double helices. There are many variants of the tetraloop. The published ones include ANYA,
CUYG,
GNRA,
UNAC
and UNCG.
Three types of tetraloops are ...
" and is particularly stable due to the base-stacking interactions of its component nucleotides. Therefore, such loops can form on the microsecond time scale.
Structural contexts
Stem-loops occur in pre-
microRNA structures and most famously in
transfer RNA, which contain three true stem-loops and one stem that meet in a cloverleaf pattern. The anticodon that recognizes a
codon during the
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
process is located on one of the unpaired loops in the tRNA. Two nested stem-loop structures occur in RNA
pseudoknots, where the loop of one structure forms part of the second stem.
Many
ribozymes also feature stem-loop structures. The self-cleaving
hammerhead ribozyme contains three stem-loops that meet in a central unpaired region where the cleavage site lies. The hammerhead ribozyme's basic secondary structure is required for self-cleavage activity.
Hairpin loops are often elements found within the
5'UTR
The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of t ...
of prokaryotes. These structures are often bound by proteins or cause the attenuation of a transcript in order to regulate translation.
The mRNA stem-loop structure forming at the
ribosome binding site may control an initiation of
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
.
Stem-loop structures are also important in
prokaryotic rho-independent transcription termination. The hairpin loop forms in an
mRNA strand during transcription and causes the
RNA polymerase to become dissociated from the DNA template strand. This process is known as rho-independent or intrinsic termination, and the sequences involved are called terminator sequences.
See also
*
Dyad symmetry
*
Inverted repeat
*
Kissing stem-loop
*
Palindromic sequence
*
Repeat sequences
*
Satellite DNA
*
5'UTR
The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of t ...
References
{{DEFAULTSORT:Stem-Loop
RNA
DNA