Nucleic acid secondary structure

Source: Wikipedia, the free encyclopedia.
This article is about secondary structure in nucleic acid. For the article about secondary structure in protein, see Protein secondary structure.
Nucleic acid primary structureNucleic acid double helixStem-loopPseudoknotNucleic acid tertiary structureNucleic acid quaternary structure
The image above contains clickable links
The image above contains clickable links
Interactive image of nucleic acid structure (primary, secondary, tertiary, and quaternary) using DNA helices and examples from the VS ribozyme and telomerase and nucleosome. (PDB: ADNA, 1BNA, 4OCB, 4R4V, 1YMO, 1EQZ​)


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.[1]
The
hydroxyl group in the ribose sugar.[citation needed
]

In a non-biological context, secondary structure is a vital consideration in the nucleic acid design of nucleic acid structures for DNA nanotechnology and DNA computing, since the pattern of basepairing ultimately determines the overall structure of the molecules.

Fundamental concepts

Base pairing

Top, an AT base pair demonstrating two intermolecular hydrogen bonds; bottom, a GC base pair demonstrating three intermolecular hydrogen bonds.
Main article: Base pair

In

translation
. Some DNA- or RNA-binding enzymes can recognize specific base pairing patterns that identify particular regulatory regions of genes. Hydrogen bonding is the chemical mechanism that underlies the base-pairing rules described above. Appropriate geometrical correspondence of hydrogen bond donors and acceptors allows only the "right" pairs to form stably. DNA with high GC-content is more stable than DNA with low GC-content, but contrary to popular belief, the hydrogen bonds do not stabilize the DNA significantly and stabilization is mainly due to stacking interactions.[2]

The larger nucleobases, adenine and guanine, are members of a class of doubly ringed chemical structures called purines; the smaller nucleobases, cytosine and thymine (and uracil), are members of a class of singly ringed chemical structures called pyrimidines. Purines are only complementary with pyrimidines: pyrimidine-pyrimidine pairings are energetically unfavorable because the molecules are too far apart for hydrogen bonding to be established; purine-purine pairings are energetically unfavorable because the molecules are too close, leading to overlap repulsion. The only other possible pairings are GT and AC; these pairings are mismatches because the pattern of hydrogen donors and acceptors do not correspond. The GU wobble base pair, with two hydrogen bonds, does occur fairly often in RNA.

Nucleic acid hybridization

Main article: Nucleic acid thermodynamics

Hybridization is the process of

double helix. Melting is the process by which the interactions between the strands of the double helix are broken, separating the two nucleic acid strands. These bonds are weak, easily separated by gentle heating, enzymes, or physical force. Melting occurs preferentially at certain points in the nucleic acid.[3] T and A rich sequences are more easily melted than C and G rich regions. Particular base steps are also susceptible to DNA melting, particularly T A and T G base steps.[4] These mechanical features are reflected by the use of sequences such as TATAA
at the start of many genes to assist RNA polymerase in melting the DNA for transcription.

Strand separation by gentle heating, as used in PCR, is simple providing the molecules have fewer than about 10,000 base pairs (10 kilobase pairs, or 10 kbp). The intertwining of the DNA strands makes long segments difficult to separate. The cell avoids this problem by allowing its DNA-melting enzymes (helicases) to work concurrently with topoisomerases, which can chemically cleave the phosphate backbone of one of the strands so that it can swivel around the other. Helicases unwind the strands to facilitate the advance of sequence-reading enzymes such as DNA polymerase.

Secondary structure motifs

Further information: Structural motif § In nucleic acids
The main nucleic acid helix structures (A-, B- and Z-form)

Nucleic acid secondary structure is generally divided into helices (contiguous base pairs), and various kinds of loops (unpaired nucleotides surrounded by helices). Frequently these elements, or combinations of them, are further classified into additional categories including, for example, tetraloops, pseudoknots, and stem-loops. Topological approaches can be used to categorize and compare complex structures that arise from combining these elements in various arrangements.

Double helix

Main article: Nucleic acid double helix

The double helix is an important tertiary structure in nucleic acid molecules which is intimately connected with the molecule's secondary structure. A double helix is formed by regions of many consecutive base pairs.

The nucleic acid double helix is a spiral polymer, usually right-handed, containing two

B-DNA, and Z-DNA
, while RNA double helices have structures similar to the A form of DNA.

Stem-loop structures

An RNA stem-loop secondary structure
Main article: Stem-loop

The secondary structure of nucleic acid molecules can often be uniquely decomposed into stems and loops. The stem-loop structure (also often referred to as an "hairpin"), in which a base-paired helix ends in a short unpaired loop, is extremely common and is a building block for larger structural motifs such as cloverleaf structures, which are four-helix junctions such as those found in transfer RNA. Internal loops (a short series of unpaired bases in a longer paired helix) and bulges (regions in which one strand of a helix has "extra" inserted bases with no counterparts in the opposite strand) are also frequent.

There are many secondary structure elements of functional importance to biological RNAs; some famous examples are the Rho-independent terminator stem-loops and the tRNA cloverleaf. Active research is on-going to determine the secondary structure of RNA molecules, with approaches including both experimental and computational methods (see also the List of RNA structure prediction software).

Pseudoknots

Main article: Pseudoknot
An RNA pseudoknot structure. For example, the RNA component of human telomerase.[7]

A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. Pseudoknots fold into knot-shaped three-dimensional conformations but are not true topological knots. The base pairing in pseudoknots is not well nested; that is, base pairs occur that "overlap" one another in sequence position. This makes the presence of general pseudoknots in nucleic acid sequences impossible to predict by the standard method of dynamic programming, which uses a recursive scoring system to identify paired stems and consequently cannot detect non-nested base pairs with common algorithms. However, limited subclasses of pseudoknots can be predicted using modified dynamic programs.[8] Newer structure prediction techniques such as

stochastic context-free grammars
are also unable to consider pseudoknots.

Pseudoknots can form a variety of structures with catalytic activity[9] and several important biological processes rely on RNA molecules that form pseudoknots. For example, the RNA component of the human telomerase contains a pseudoknot that is critical for its activity.[7] The hepatitis delta virus ribozyme is a well known example of a catalytic RNA with a pseudoknot in its active site.[10][11] Though DNA can also form pseudoknots, they are generally not present in standard physiological conditions.

Secondary structure prediction

Main article: Nucleic acid structure prediction
Further information: List of RNA structure prediction software

Most methods for nucleic acid secondary structure prediction rely on a nearest neighbor thermodynamic model.

stochastic context-free grammars
can also be used to predict nucleic acid secondary structure.

For many RNA molecules, the secondary structure is highly important to the correct function of the RNA — often more so than the actual sequence. This fact aids in the analysis of

microRNAs
have canonical long stem-loop structures interrupted by small internal loops.

RNA secondary structure applies in

teleosts the RNA splicing process can still occur on certain genes in the absence of U2AF2. This may be because 10% of genes in zebrafish have alternating TG and AC base pairs at the 3' splice site (3'ss) and 5' splice site (5'ss) respectively on each intron, which alters the secondary structure of the RNA. This suggests that secondary structure of RNA can influence splicing, potentially without the use of proteins like U2AF2 that have been thought to be required for splicing to occur.[15]

Secondary structure determination

RNA secondary structure can be determined from atomic coordinates (tertiary structure) obtained by X-ray crystallography, often deposited in the Protein Data Bank. Current methods include 3DNA/DSSR[16] and MC-annotate.[17]

See also

References

  1. PMID 14990744
    .
  2. PMID 16449200
    .
  3. PMID 3459152
    .
  4. ^ Richard Owczarzy (2008-08-28). "DNA melting temperature - How to calculate it?". High-throughput DNA biophysics. owczarzy.net. Archived from the original on 2015-04-30. Retrieved 2008-10-02.
  5. ISBN 978-0-8153-4105-5
    .
  6. PMID 6236744
    .
  7. ^
    PMID 15849264
    .
  8. S2CID 2228845
    .
  9. PMID 15941360
    .
  10. S2CID 4359811
    .
  11. PMID 7574482
    .
  12. PMID 9778347
    .
  13. PMID 15123812
    .
  14. PMID 2468181
    .
  15. PMID 26566657
    .
  16. PMID 26184874
    .
  17. ^ "MC-Annotate". www-lbit.iro.umontreal.ca.

External links

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