Stem-loop

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An example of an RNA stem-loop Stem-loop.svg
An example of an RNA stem-loop

Stem-loops are nucleic acid secondary structural elements which form via intramolecular base pairing in single-stranded DNA or RNA. They are also referred to as hairpins or hairpin loops. A stem-loop occurs when two regions of the same nucleic acid strand, usually complementary in nucleotide sequence, base-pair to form a double helix that ends in a loop of unpaired nucleotides.

Contents

Stem-loops are most commonly found in RNA, and are a key building block of many RNA secondary structures. Stem-loops 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. [1]

Formation and stability

The formation of a stem-loop is dependent on the stability of the 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 and cytosine 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 DNA. Base stacking interactions, which align the pi bonds 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. Optimal loop length tends to be about 4-8 bases long; loops that are fewer than three bases long are sterically impossible and thus do not form, and large loops with no secondary structure of their own (such as pseudoknot pairing) are unstable. One common loop with the sequence UUCG is known as the "tetraloop," and is particularly stable due to the base-stacking interactions of its component nucleotides. Therefore, such loops can form on the microsecond time scale. [2]

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 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 of prokaryotes. These structures are often bound by proteins or cause the attenuation of a transcript in order to regulate translation. [3]

The mRNA stem-loop structure forming at the ribosome binding site may control an initiation of translation. [4] [5]

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

Related Research Articles

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<span class="mw-page-title-main">Protein biosynthesis</span> Assembly of proteins inside biological cells

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<span class="mw-page-title-main">RNA</span> Family of large biological molecules

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<span class="mw-page-title-main">Directionality (molecular biology)</span> End-to-end chemical orientation of a single strand of nucleic acid

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<span class="mw-page-title-main">Hammerhead ribozyme</span>

The hammerhead ribozyme is an RNA motif that catalyzes reversible cleavage and ligation reactions at a specific site within an RNA molecule. It is one of several catalytic RNAs (ribozymes) known to occur in nature. It serves as a model system for research on the structure and properties of RNA, and is used for targeted RNA cleavage experiments, some with proposed therapeutic applications. Named for the resemblance of early secondary structure diagrams to a hammerhead shark, hammerhead ribozymes were originally discovered in two classes of plant virus-like RNAs: satellite RNAs and viroids. They are also known in some classes of retrotransposons, including the retrozymes. The hammerhead ribozyme motif has been ubiquitously reported in lineages across the tree of life.

<span class="mw-page-title-main">Hairpin ribozyme</span> Enzymatic section of RNA

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<span class="mw-page-title-main">Intrinsic termination</span>

Intrinsic, or rho-independent termination, is a process to signal the end of transcription and release the newly constructed RNA molecule. In bacteria such as E. coli, transcription is terminated either by a rho-dependent process or rho-independent process. In the Rho-dependent process, the rho-protein locates and binds the signal sequence in the mRNA and signals for cleavage. Contrarily, intrinsic termination does not require a special protein to signal for termination and is controlled by the specific sequences of RNA. When the termination process begins, the transcribed mRNA forms a stable secondary structure hairpin loop, also known as a stem-loop. This RNA hairpin is followed by multiple uracil nucleotides. The bonds between uracil (rU) and adenine (dA) are very weak. A protein bound to RNA polymerase (nusA) binds to the stem-loop structure tightly enough to cause the polymerase to temporarily stall. This pausing of the polymerase coincides with transcription of the poly-uracil sequence. The weak adenine-uracil bonds lower the energy of destabilization for the RNA-DNA duplex, allowing it to unwind and dissociate from the RNA polymerase. Overall, the modified RNA structure is what terminates transcription.

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<span class="mw-page-title-main">Tetraloop</span>

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.

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<span class="mw-page-title-main">Nucleic acid structure</span> Biomolecular structure of nucleic acids such as DNA and RNA

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<span class="mw-page-title-main">Nucleic acid secondary structure</span>

Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNAs and RNAs tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.

<span class="mw-page-title-main">Complementarity (molecular biology)</span> Lock-and-key pairing between two structures

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<span class="mw-page-title-main">Kissing stem-loop</span>

In genetics, a kissing stem-loop, or kissing stem loop interaction, is formed in ribonucleic acid (RNA) when two bases between two hairpin loops pair. These intra- and intermolecular kissing interactions are important in forming the tertiary or quaternary structure of many RNAs.

<span class="mw-page-title-main">Hatchet ribozyme</span> Self-cleaving ribozyme

Background: The hatchet ribozyme is an RNA structure that catalyzes its own cleavage at a specific site. In other words, it is a self-cleaving ribozyme. Hatchet ribozymes were discovered by a bioinformatics strategy as RNAs Associated with Genes Associated with Twister and Hammerhead ribozymes, or RAGATH.

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Coronavirus genomes are positive-sense single-stranded RNA molecules with an untranslated region (UTR) at the 3′ end which is called the 3′ UTR. The 3′ UTR is responsible for important biological functions, such as viral replication. The 3′ UTR has a conserved RNA secondary structure but different Coronavirus genera have different structural features described below.

References

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