Nucleic Acids

Babak Nami
Department of Medical Genetics Seluk Faculty of Medicine Seluk University

Definition
Nucleic acids are biological molecules essential for life, and include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).

History of Nucleic Acids

1869. Meischer isolated nucleic acids, which he called nuclein. 1881. Zacharis identified nuclein with chromatin. 1884. Hertwig suggested the role of nuclein in heredity. 1899. Altmann identified that nuclein is an acid and used the term nucleic acid to replace nuclein. 1880. Fischer identified pyrimidines and purines. 1884. Kossel recognized that histones and protamines were associated with nucleic acids.

History of Nucleic Acids (con)

1938. Astbury and Bell showed that the bases in a DNA molecule are stacked one above the other, and lie with their planes perpendicular to the long axis of the molecule. 1944. Avery, MacLeod and McCarty presented first evidence that DNA is the genetic material. 1947. Chargaff showed that DNA contains equal proportions of purines and pyrimidines.

History of Nucleic Acids (con)

1950. Wilkins and coworkers showed that the purine and pyrimidine bases are placed regularly along the DNA molecule at a distance of 3.4 A. The molecules are twisted into a helix with one complete turn every 34 A. 1952. Furberg suggested that the DNA molecule is formed by the coiling of a single nucleic acid chain. 1952. Hershey and Chase showed that in the T2 virus DNA is the sole carrier of genetic information form parent to offspring.

1953. Pauling and Corey suggested that the DNA molecule consists of three chains twisted to form a helix.
1953. Watson and Crick presented the now famous double helix model of DNA.

History of Nucleic Acids (con)

1958. Meselson and Stahl demonstrated that DNA replicates in a semiconservative manner. 1958. Sinsheimer showed that the genetic material of the bacteriophage X174 is a single strand of DNA.

1961. Jacob and Monod postulated the presence and function of messenger RNA in protein synthesis and proposed the operon concept.
1964. Holley described the nucleotide sequence of a transfer RNA molecule from yeast. 1969. Shapiro published the first picture of an isolated gene (lac duplex).

Structure of Nucleic Acids

A Structure for Nucleic Acid was an article published by James D. Watson and Francis Crick in the Scientific journal Nature in its 171st volume on pages 737738 (dated April 25, 1953). It was the first publication which described the discovery of the double helix structure of DNA. DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are polymers of nucleotides linked in a chain through phosphodiester bonds. In biological systems, they serve as information carrying molecules.

Structure of Nucleic Acids (con)

Nucleotides are the building blocks of all nucleic acids. Nucleotides have a distinctive structure composed of three components covalently bound together: A nitrogen-containing "base" either a pyrimidine (one ring) or purine (two rings) A 5-carbon sugar, ribose or deoxyribose A phosphate group

Structure of Nucleic Acids (con)

The combination of a base and sugar is called a nucleoside. Nucleotides also exist in activated forms containing two or three phosphates, called nucleotide diphosphates or triphosphates. If the sugar in a nucleotide is deoxyribose, the nucleotide is called a deoxynucleotide. if the sugar is ribose, the term ribonucleotide is used.

Structure of Nucleic Acids (con)

understanding this concept and nomenclature is critical to understanding polarity of nucleic acids, as discussed below. The 5' carbon has an attached phosphate group, while the 3' carbon has a hydroxyl group. There are five common bases, and four are generally represented in either DNA or RNA. Those bases and their corresponding nucleosides are described in the following table:

Structure of Nucleic Acids (con)

Structure of Nucleic Acids (con)

Another useful way to categorize nucleotide bases is as purines (A and G) versus pyrimidines (C, T and U).

Structure of Nucleic Acids (con)

In all nucleic acid formations, the process involves forming phosphodiester bonds between the 3' carbon of one nucleotide and the 5' carbon of another nucleotide. This leads to formation of the so-called "sugar-phosphate backbone", from which the bases project.

Structure of Nucleic Acids (con)

Most DNA exists in the famous form of a double helix, in which two linear strands of DNA are wound around one another. The major force promoting formation of this helix is complementary base pairing: A's form hydrogen bonds with T's (or U's in RNA), and G's form hydrogen bonds with C's. If we mix two ATGC's together, the following duplex will form:

Structure of Nucleic Acids (con)

Structure of Nucleic Acids (con)

Note two very important features: The two strands of DNA are arranged antiparallel to one another: viewed from left to right the "top" strand is aligned 5' to 3', while the "bottom" strand is aligned 3' to 5'. This is always the case for duplex nucleic acids. G-C base pairs have 3 hydrogen bonds, whereas A-T base pairs have 2 hydrogen bonds: one consequence of this disparity is that it takes more energy (e.g. a higher temperature) to disrupt GC-rich DNA than AT-rich DNA.

Structure of Nucleic Acids (con)

RNAs are usually single stranded. but many RNA molecules have secondary structure in which intramolecular loops are formed by complementary base pairing. Base pairing in RNA follows exactly the same principles as with DNA: the two regions involved in duplex formation are antiparallel to one another, and the base pairs that form are A-U and G-C.

Structure of Nucleic Acids (con)

DNA
DNA, is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organism (with the exception of RNA viruses). The main role of DNA molecular is the longterm storage of information, and transferring the information for next generations.

Structure of DNA
In DNA, the amount of guanin is equal to cytosine and the amount of adenin is equal to thymine. The A:T and C:G pairs are structurally similar. The base pairs are held together by hydrogen band, a type of chemical attraction that is easy to break and easy to reform. After realizing the structural similarity of the A:T and C:G pairs, Watson and Crick soon produced their double helix model of DNA with the hydrogen bonds at the core of the helix providing a way to unzip the two complementary strands for easy replication.

Structure of DNA
.

1953

1999

James D. Watson

Francis Crick

Structure of DNA
The structure of DNA of all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34 Angstrom (3.4 nanometres) and a diameter of 20 Angstrom (2.0 nanometres). Genome of an human somatic cell contain about 3 billions nucleotides which makeup DNA with 2 meters long.

Structure of DNA

Alternate DNA structures

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms.

B-DNA structure
Watson-Crick -helix B-DNA structure (very regular) came from model building based on xray diffraction data from DNA fibers consisting of parallel oriented DNA molecules. REAL STRUCTURE: X-ray structure of crystals of 12-bp DNA (dodecamer) looks mostly like Watson-Crick B-form helix, but there are some irregularities compared to W-C model. the B-DNA form is most common under the conditions found in cells.

B-DNA structure

B-DNA structure
Right handed double helix. 10 base pairs and 34 Angstrom per turn. Bases are perpendicular to helical axis, 3.4 Angstrom rise per base. Bases are tilted 1o. clearly defined major and minor grooves, with the major grooves being 23.7 Angstrom across and the minor groove being only 12 Angstrom. C2'-endo pucker preferred, and the bases adopt the anti- configuration.

A-DNA structure
Right handed double helix. 11 bases pairs and 25 Angstrom per turn. Bases are tilted 20o No defined major or minor grooves. 2.9 Angstrom rise per base. C3'-endo pucker preferred, bases adopt the anti configuration.

Z-DNA structure
Left handed double helix. 12 bp per turn. Irregular helix. Bases irregularly tilted off the perpendicular axis. ~7.5 Angstrom rise per dinucleotide repeat Some discernable irregularly defined grooves. Bases alternate between both the C2' and C3'endo pucker conformation and the anti and syn configuration.

Comparison of DNA forms

Comparison DNA form

Function of DNA
DNA holds the instructions for an organism's development and reproduction. DNA is responsible for all the biological functions through genes. DNA holds the code for proteins, which are complex molecules that do huge amounts of work around our body. DNA in a gene is transmitted from one generation to another generation, by the process of inheritance.

DNA Packaging
The haploid human genome contains approximately 3 billion base pairs of DNA. Of course, most cells in the body (except for female ova and male sperm) are diploid, with 23 pairs of chromosomes. That makes a total of 6 billion base pairs of DNA per cell. Because each base pair is around 0.34 nanometers long, each diploid cell therefore contains about 2 meters of DNA [(0.34 10-9) (6 109)].

DNA Packaging
Moreover, it is estimated that the human body contains about 50 trillion cells which works out to 100 trillion meters of DNA per human. Now, consider the fact that the Sun is 150 billion meters from Earth. This means that each of us has enough DNA to go from here to the Sun and back more than 300 times, or around Earth's equator 2.5 million times! How is this possible?

DNA Packaging (the histones)

The answer to this question lies in the fact that certain proteins compact chromosomal DNA into the microscopic space of the eukaryotic nucleus. These proteins are called histones, and the resulting DNA-protein complex is called chromatin. Thus, within the nucleus, histones provide the energy (mainly in the form of electrostatic interactions) to fold DNA. As a result, chromatin can be packaged into a much smaller volume than DNA alone.

DNA Packaging (the histones)

Histones are a family of small, positively charged proteins termed H1, H2A, H2B, H3, and H4 (Van Holde, 1988). DNA is negatively charged, due to the phosphate groups in its phosphate-sugar backbone, so histones bind with DNA very tightly.

DNA Packaging (the nucleosome)

The basic repeating structural (and functional) unit of chromatin is the nucleosome, which contains nine histone proteins and about 166 base pairs of DNA (Van Holde, 1988; Wolffe, 1999). The observation by electron microscopists that chromatin appeared similar to beads on a string provided an early clue that nucleosomes exist (Olins and
Olins, 1974; Woodcock et al., 1976).

DNA Packaging (the nucleosome)

Today, researchers know that nucleosomes are structured as follows: Two each of the histones H2A, H2B, H3, and H4 come together to form a histone octamer, which binds and wraps about 1.7 turns of DNA, or about 146 base pairs. The addition of one H1 protein wraps another 20 base pairs, resulting in two full turns around the octamer. His joining DNA is referred to as linker DNA.

DNA Packaging (the chromatine)

The packaging of DNA into nucleosomes shortens the fiber length about sevenfold with 30 nanometers in diameter. In other words, a piece of DNA that is 2 meter long will become just 30 centimeters long. Despite this shortening, the 30 cm chromatin is still much too long to fit into the nucleus, which is typically only 10 to 20 microns in diameter. Therefore, chromatin is further coiled into an even shorter.

DNA Packaging (the chromosome)

When eukaryotic cells divide, genomic DNA must be equally partitioned into both daughter cells. To accomplish this, the DNA becomes highly compacted into the classic metaphase chromosomes that can be seen with a light microscope. Once a cell has divided, its chromosomes uncoil again.

DNA Packaging (the chromosome)

Comparing the length of metaphase chromosomes to that of naked DNA, the packing ratio of DNA in metaphase chromosomes is approximately 10,000:1 (depending on the chromosome). This can be thought of as akin to taking a rope as long as a football field and compacting it down to less than half an inch.

RNA
Ribonucleic acid (RNA) is a biologically important type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nitrogenous base, a ribose sugar, and a phosphate. some RNA molecules play an active role in cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. The most important active processes is protein synthesis (mRNA, tRNA, rRNA)

RNA
RNAs are highly structured, therefore, can achieve chemical catalysis, like enzymes. For instance, determination of the structure of the ribosome an enzyme that catalyzes peptide bond formation revealed that its active site is composed entirely of RNA.

History of RNA
1930 1950 RNA and DNA have distinct chemical properties 1951 - 1965 Messenger RNA (mRNA) carries genetic information that directs protein synthesis. Ribosomes make proteins Transfer RNA (tRNA) is the physical link between RNA and protein The genetic code is solved RNA polymerase is purified

History of RNA
1966 1975 First complete genomic nucleotide sequence Evolutionary variation of homologous RNA sequences reveals folding patterns Reverse transcriptase can copy RNA into DNA Ribosomal RNA (rRNA) sequences provide a record of the evolutionary history of all life forms Non-encoded nucleotides are added to the ends of RNA molecules

History of RNA
1976 - 1985 Small RNA molecules are abundant in the eukaryotic nucleus Genes are commonly interrupted by introns that must be removed by RNA splicing Alternative pre-mRNA splicing generates multiple proteins from a single gene Discovery of catalytic RNA (ribozymes)

History of RNA
1986 - 2000 RNA sequences can be edited within cells Telomerase uses a built-in RNA template to maintain chromosome ends Ribosomal RNA catalyzes peptide bond formation Combinatorial selection of RNA molecules enables in vitro evolution

History of RNA
2001 - present Many mobile DNA elements use an RNA intermediate Riboswitches bind cellular metabolites and control gene expression Small RNA molecules regulate gene expression by post-transcriptional gene silencing Noncoding RNA controls epigenetic phenomena

RNA, Comparison with DNA

RNA and DNA are both nucleic acids, but differ in three main ways: 1. unlike DNA, which is, in general, double stranded, RNA is a single stranded molecule in many of its biological roles and has a much shorter chain of nucleotides. 2. while DNA contains deoxyribose, RNA contains ribose (in deoxyribose there is no hydroxyl group attached to the pentose ring in the 2 position). These hydroxyl groups make RNA less stable than DNA because it is more prone to hydrolysis. 3. the complementary base to adenine is not thymine, as it is in DNA, but rather uracil, which is an unmethylated form of thymine.

RNA structure
An important structural feature of RNA that distinguishes it from DNA is the presence of a hydroxyl group at the 2' position of the ribose sugar. The presence of this functional group causes the helix to adopt the A-form geometry rather than the B-form most commonly observed in DNA. This results in a very deep and narrow major groove and a shallow and wide minor groove.

RNA structure
A second consequence of the presence of the 2'hydroxyl group is that in conformationally flexible regions of an RNA molecule (that is, not involved in formation of a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the backbone. Pseudouridine (), in which the linkage between uracil and ribose is changed from a CN bond to a CC bond, and ribothymidine (T) are found in various places (the most notable ones being in the TC loop of tRNA). Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine (I). Inosine plays a key role in the wobble hypothesis of the genetic code.

Wobble hypothesis
A wobble base pair is a non-Watson-Crick base pairing between two nucleotides in RNA molecules. The four main wobble base pairs are guanineuracil, inosine-uracil, inosine-adenine and inosine-cytosine.

Wobble hypothesis
The fact that there are 61 amino-acid-coding codons and roughly 40 tRNA molecules presented a problem; in 1966 Francis Crick proposed the Wobble hypothesis to account for this. He postulated that the 5' base on the anti-codon was not as spatially confined as the other two bases, and could thus have non-standard base pairing. This would account for 60 codons for 40 tRNA. As an example yeast tRNAPhe has the anticodon 5'GmAA-3' and can recognize the codons 5'-UUC-3' and 5'-UUU-3'. It is, therefore, possible for nonWatson-Crick base pairing to occur at the third codon position, i.e. the 3' nucleotide of the mRNA codon and the 5' nucleotide of the tRNA anticodon.

Isoleusine

tRNA

U A I A U A A U U A U C
mRNA

RNA folding
RNA is single strand normally but intra-strand base pairing will produce structures such as the one shown below:

RNA folding
The stability of a particular secondary structure is a function of several constraints: 1. The number of GC versus AU and GU base pairs. (Higher energy bonds form more stable structures.) 2. The number of base pairs in a stem region. (Longer stems result in more bonds.) 3. The number of base pairs in a hairpin loop region. (Formation of loops with more than 10 or less than 5 bases requires more energy.) 4. The number of unpaired bases, whether interior loops or bulges. (Unpaired bases decrease the stability of the structure.).

Messenger RNA
Messenger RNA (mRNA) is the RNA that carries information from DNA to the ribosome, the sites of protein synthesis (translation) in the cell.

Messenger RNA
During transcription, RNA pol makes a copy of a gene from the DNA to mRNA as needed. This process is similar in eukaryotes and prokaryotes. One notable difference, however, is that prokaryotic RNA polymerase associates with mRNA processing enzymes during transcription so that processing can proceed quickly after the start of transcription. The short-lived, unprocessed or partially processed, product is termed pre-mRNA; once completely processed, it is termed mature mRNA.

Messenger RNA
Splicing is the process by which pre-mRNA is modified to remove certain stretches of noncoding sequences called introns; the stretches that remain include protein-coding sequences and are called exons. Splicing is usually performed by an RNA-protein complex called the spliceosome, but some RNA molecules are also capable of catalyzing their own splicing.

Messenger RNA
Polyadenylation: in eukaryotic organisms, most messenger RNA molecules are polyadenylated at the 3' end. The poly (A) and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation.

Messenger RNA (Structure)

5' cap: The 5' cap is a modified guanine nucleotide added to the "front" of the pre-mRNA using a 5'-5'-triphosphate linkage. This modification is critical for recognition and proper attachment of mRNA to the ribosome, as well as protection from 5' exonucleases. It may also be important for other essential processes, such as splicing and transport.

Messenger RNA (Structure)

Coding regions: Coding regions are composed of codons, which are decoded and translated (in eukaryotes usually into one and in prokaryotes usually into several) proteins by the ribosome. Coding regions begin with the start codon and end with a stop codon. Generally, the start codon is an AUG triplet and the stop codon is UAA, UAG, or UGA.

Messenger RNA (Structure)

5' UTR and 3' UTR: Untranslated regions (UTRs) are sections of the mRNA before the start codon and after the stop codon that are not translated, termed the five prime untranslated region (5' UTR) and three prime untranslated region (3' UTR), respectively. These regions are transcribed with the coding region and thus are exonic as they are present in the mature mRNA.

Messenger RNA (Structure)

Poly(A) tail: The 3' poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the 3' end of the pre-mRNA. This tail promotes export from the nucleus and translation, and protects the mRNA from degradation.

Messenger RNA (Transport)

Another difference between eukaryotes and prokaryotes is mRNA transport. eukaryotic mRNAs must be exported from the nucleus to the cytoplasm. Mature mRNAs are recognized by their processed modifications and then exported through the nuclear pore. In neurons mRNA must be transported from the soma to the dendrites where local translation occurs in response to external stimuli. Many messages are marked with so-called "zip codes" which targets their transport to a specific location.

Messenger RNA (Transport)

Messenger RNA
Monocistronic versus polycistronic mRNA An mRNA molecule is said to be monocistronic when it contains the genetic information to translate only a single protein. This is the case for most of the eukaryotic mRNAs. On the other hand, polycistronic mRNA carries the information of several genes, which are translated into several proteins. These proteins usually have a related function and are grouped and regulated together in an operon. Most of the mRNA found in bacteria and archea are polycistronic.

Messenger RNA
mRNA circularization: In eukaryotes it is thought that mRNA molecules form circular structures due to an interaction between the cap binding complex and poly (A)binding protein. Circularization is thought to promote recycling of ribosomes on the same message leading to efficient translation.

Transfer RNA
Transfer RNA (tRNA) is RNA that transfers a specific active amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. tRNA has a 3 terminal site for amino acid attachment. Each type of tRNA molecule can be attached to only one type of amino acid, but because the genetic code contains multiple codons that specify the same amino acid, tRNA molecules bearing different anticodons may also carry the same amino acid.

Transfer RNA
The existence of tRNA was first hypothesized by Francis Crick. In 1965, a publication by Robert W. Holley reported the primary structure and suggested three secondary structures. in 1974 two independent groups, Kim sung-Hou working under Alexander Rich and a British group headed by Aaron Klug, published the Xray crystallography findings within a year.

Transfer RNA (Structure)

The structure of tRNA can be decomposed into its primary structure, its secondary structure and its tertiary structure (all tRNAs have a similar L-shaped 3D structure that allows them to fit into the P and A sites of the ribosome).

Transfer RNA (Aminoacylation)

Aminoacylation is the process of adding an aminoacyl group to a compound. It produces tRNA molecules with their CCA 3' ends covalently linked to an amino acid.
amino acid + ATP aminoacyl-AMP + PPi aminoacyl-AMP + tRNA aminoacyl-tRNA + AMP

Transfer RNA (Binding to ribosome)

The ribosome has three binding sites for tRNA molecules: the A (aminoacyl), P (peptidyl), and E (exit) sites. During translation the A site binds an incoming aminoacyl-tRNA as directed by the codon currently occupying this site. The A site only works after the first aminoacyl-tRNA has attached to the P site. The P-site codon is occupied by peptidyl-tRNA that is a tRNA with multiple amino acids attached as a long chain. The P site is actually the first to bind to aminoacyl tRNA. This tRNA in the P site carries the chain of amino acids that has already been synthesized. The E site is occupied by the empty tRNA as it's about to exit the ribosome.

Ribosomal RNA
rRNA is the RNA component of the ribosome. Ribosomal RNA provides a mechanism for decoding mRNA into amino acids and interacts with tRNAs during translation by providing peptidyl transferase activity. The tRNAs bring the necessary amino acids corresponding to the appropriate mRNA codon. The ribosomal RNAs form two subunits, the large subunit (LSU) and small subunit (SSU). mRNA is sandwiched between the small and large subunits and the ribosome catalyzes the formation of a peptide bond between the 2 amino acids that are contained in the rRNA.

Molecular structure of the 50S subunit of prokaryote cells. Proteins are shown in blue and RNA in orange.

Signal recognition particle RNA

signal recognition particle RNA, also known as 7SL, 6S, ffs, or 4.5S RNA, is the RNA component of the signal recognition particle (SRP) ribonucleoprotein complex. SRP is a universally conserved ribonucleoprotein that directs the traffic of proteins within the cell and allows them to be secreted. The SRP RNA, together with one or more SRP proteins contributes to the binding and release of the signal peptide. The RNA and protein components of this complex are highly conserved but do vary between the different kingdoms of life.

Transfer-messenger RNA
Transfer-messenger RNA (abbreviated tmRNA, also known as 10Sa RNA and by its genetic name SsrA) is a bacterial RNA molecule with dual tRNA -like and mRNA-like properties.

Small nuclear RNA

snRNA is a class of small RNA molecules that are found within the nucleus of eukaryotic cells. They are transcribed by RNA pol II or RNA pol III and are involved in a variety of important processes such as RNA splicing, regulation of transcription factors (7skRNA) or RNA pol II (B2 RNA), and maintaining the telomerase.

Small nucleolar RNA

snoRNAs are a class of small RNA molecules that primarily guide chemical modifications of other RNAs, mainly ribosomal RNAs, transfer RNAs and small nuclear RNAs.

SmY RNA
SmY RNAs are a family of small nuclear RNAs found in some species of nematode worms. They are thought to be involved in mRNA transsplicing.

Small Cajal body-specific RNA

scaRNAs are a class of small nucleolar RNAs (snoRNAs) which specifically localise to the Cajal body, a nuclear organelle involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs or snurps). ScaRNAs guide the modification (methylation and pseudouridylation) of RNA pol II transcribed spliceosomal RNAs U1, U2, U4, U5 and U12.

Guide RNA
gRNA are the RNAs that guide the insertion or deletion of uridine residues into mitochondrial mRNAs in kinetoplastid protists in a process known as RNA editing.

RNase P
Ribonuclease P is a type of Ribonuclease which cleaves RNA. RNase P is unique from other RNases in that it is a ribozyme a ribonucleic acid that acts as a catalyst in the same way that a protein based enzyme would. Its function is to cleave off an extra, or precursor, sequence of RNA on tRNA molecules.

RNase MRP
RNase MRP is an enzymatically active ribonucleoprotein with two distinct roles in eukaryotes. In mitochondria it plays a direct role in the initiation of mtDNA replication. In the nucleus it is involved in precursor rRNA processing, where it cleaves the internal transcribed spacer 1 between 18S and 5.8S rRNAs.

Y RNA
Y RNAs are small non-coding RNA components of the Ro ribonucleoprotein particle (Ro RNP). The Ro RNP was first identified by Lerner et al.. as a target of autoimmune antibodies in patients with systemic lupus erythematosus.

Telomerase RNA
Telomerase RNA component, also known as TERC, is an RNA gene found in eukaryotes, that is a component of telomerase used to extend telomerase. Telomerase RNAs differ greatly in sequence and structure between vertebrates, ciliates and yeasts, but they share a 5pseudoknot structure close to the template sequence.

Vertebrate telomerase RNA

Antisense RNA
Antisense RNA is a single-stranded RNA that is complementary to a messenger RNA (mRNA) strand transcribed within a cell. Antisense RNA may be introduced into a cell to inhibit translation of a complementary mRNA by base pairing to it and physically obstructing the translation machinery.

Cis-natural antisense transcript

Natural antisense transcripts (NATs) are a group of RNAs encoded within a cell that have transcript complementarity to other RNA transcripts. They have been identified in multiple eukaryotes, including humans, mice, yeast and Arabidopsis thaliana.

Long non-coding RNA

long ncRNAs or lncRNA are generally considered as non-protein coding transcripts longer than 200 nucleotides. This limit is due to practical considerations including the separation of RNAs in common experimental protocols.

MicroRNA
miRNAs are short RNA molecules, on average only 22 nucleotides long and are found in all eukaryotic cells, except fungi, algae, and marine plants. miRNAs are post-transcriptional regulators that bind to complementary sequences on target messenger RNA transcripts (mRNAs), usually resulting in translational repression and gene silencing . The human genome may encode over 1000 miRNAs, which may target about 60% of mammalian genes and are abundant in many human cell types.

Piwi-interacting RNA
piRNA is the largest class of small RNA molecules that is expressed in animal cells.

piRNA forms RNA-protein complexes through interactions with piwi proteins.

Small interfering RNA

siRNA sometimes known as short interfering RNA or silencing RNA, is a class of double strand RNAs, 20-25 nucleotides in length, that play a variety of roles in biology. The most notable role of siRNA is its involvement in the RNA interference (RNAi) pathway, where it interferes with the expression of a specific gene.

RasiRNA
Repeat associated small interfering RNA (rasiRNA) is a class of small RNA that is involved in the RNA interference (RNAi) pathway.