Non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. There are several types of ncRNAs including transfer RNA (tRNA), ribosomal RNA (rRNA), and microRNAs. tRNA transfers amino acids to sites of protein synthesis during translation. rRNA forms ribosomes and catalyzes peptide bond formation. ncRNAs are involved in many cellular processes like translation, splicing, and gene regulation. Dysregulation of ncRNAs can cause diseases like cancer.

1. NON CODING RNA
Content and references
S.no Tittle Reference Page
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Introduction.
1. RNA
http://en.wikipedia.org/wiki/Non-
coding_RNA
http://exploringorigins.org/rna.html
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Non coding RNA
Background
information
http://www.nature.com/nrg/journal/v2/
n12/abs/nrg1201-919a.html
http://www.nature.com/scitable/topicp
age/small-non-coding-rna-and-gene-
expression-1078
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Non coding RNA
1. types
http://exploringorigins.org/rna.
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mRNA
rRNA
tRNA
A text book of molecular
biology by DR P S VERMA
S Chand publishers
http://www.nobelprize.org/educ
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Functions
disease
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2. Non Coding RNA
A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated
into a protein. Less-frequently used synonyms are non-protein-coding RNA
(npcRNA), non-messenger RNA (nmRNA) and functional RNA (fRNA). The
DNA sequence from which a non-coding RNA is transcribed is often called an
RNA gene.
Non-coding RNA genes include highly abundant and functionally important RNAs
such as transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as RNAs
such as snoRNAs, microRNAs, siRNAs, snRNAs, exRNAs, and piRNAs and the
long ncRNAs that include examples such as Xist and HOTAIR (see here for a
more complete list of ncRNAs). The number of ncRNAs encoded within the
human genome is unknown; however, recent transcriptomic and bioinformatic
studies suggest the existence of thousands of ncRNAs. Since many of the newly
identified ncRNAs have not been validated for their function, it is possible that
many are non-functional.
History and discovery of RNA
Nucleic acids were first discovered in 1868 by Friedrich Miescher and by 1939
RNA had been implicated in protein synthesis. Two decades later, Francis Crick
predicted a functional RNA component which mediated translation; he reasoned
that RNA is better suited to base-pair with an mRNA transcript than a pure
The Discovery and the Origin of Non-Coding RNAs
The first ncRNAs were detected by Robert and Sharp in 1977 as micro (mi) RNAs
during the discovering that structural genes were split into exons and introns. At
first it was thought that introns have no function. However, since the discovery of
messenger RNA splicing in adenoviruses the alternative splicing of introns explain
the production of several protein in basis to the same mRNA. Thus, it is estimated
that the human genome has about 30,000 genes but about 75,000 different kinds of
proteins. The first ncRNAs with a function were described in 1993 in
Caenorhabditis elegans when it was found that small miRNAs (constituted of
about 22 nucleotides) were important for the appropriate timing of post-embryonic
development . Actually, it is known that around 98% of all transcriptional output in
humans is ncRNAs . Recently, the presence of ribozymes has been revealed in the
ncRNAs of mammalian genomes. One of these ribozymes, discontinuous
hammerhead ribozyme has been initially described in viroids and then also in
eukaryotic genomes—plants and animals

3. TYPES OF NON-GENETICRNAAND PROCESSING
According to their specific functions during the process of protein synthesis, the
following kinds of non-genetic RNA molecules have been recognized in
prokaryotic and eukaryotic cells :
(1) RibosomalRNA (rRNA)
In molecular biology, ribosomal ribonucleic acid (rRNA) is the RNA component
of the ribosome, and is essential for protein synthesis in all living organisms. In
molecular biology, ribosomal ribonucleic acid (rRNA) is the RNA component of
the ribosome, and is essential for protein synthesis in all living organisms. It
constitutes the predominant material within the ribosome, which is approximately
60% rRNA and 40% protein by weight. Ribosomes contain two major rRNAs and
50 or more proteins. The ribosomal RNAs form two subunits, the large subunit
(LSU) and small subunit (SSU). The LSU rRNA acts as a ribozyme, catalyzing
peptide bond formation. rRNA sequences are widely used for working out
evolutionary relationships among organisms, since they are of ancient origin and
are found in all known forms of life.
Ribosomal RNA (rRNA) associates with a set of proteins to form ribosomes. These
complex structures, which physically move along an mRNA molecule, catalyze the
assembly of amino acids into protein chains. They also bind tRNAs and various
accessorymolecules necessary for protein synthesis.
(II) MessengerRNA(mRNA)
The RNA molecules which are transcribed from large number of genes of the total
genome (i.e.,99 per cent genes of the total genome of E.coli) and have base
sequence complementary to DNA, carry DNA’s genetic informations for the
assembly of amino acids into the polypeptide chains (protein molecules), to the
cytoplasmic sites of protein synthesis, the ribosomes, to which they become
associated to participate in codon-anticodon interaction with tRNA, are called
informational or messenger RNAs (mRNA). The name messenger RNA has been
proposed by Jacob and Monod (1961). The molecule of a mRNA is single
stranded like the rRNA molecule and it is DNA-like in its base composition so that
GC contents of mRNA correspond to the GC contents of the genomes total DNA.
mRNA synthesis in bacteria. Messenger RNA is complementary to
chromosomalDNA; it
forms RNA-DNA hybrids after separation of the two DNA strands. Synthesis of
mRNA is accomplished with only one of the two strands of DNA, which is used as
template.

4. mRNA synthesis in eukaryotes. Transcription of eukaryotic DNA to produce
mRNA begins with the synthesis of long precursor molecules by RNA polymerase
II from the template strand of DNA. In an average cell nucleus, there is only one
molecule of RNA polymerase II per 750 nucleosomes - worth of DNA, i.e., one
enzyme molecule exists per 150,000 base pairs of DNA (Maclean and Hall, 1987).
This enzyme functions by catalyzing formation of 5'→3' phosphodiester bonds of
the RNA “backbone” by “reading” the DNA template in the 3'→5' direction. The
developing mRNA (or hn RNA) is antiparallel and its nucleotides are
complementary to those of the DNA template strand. Messenger RNA chain
growth is rapid—from 15 to 100 nucleotides per second in vitro.
Post-transcriptional modification of processing of mRNA. The immediate
product of transcription of mRNA in eukaryotes is a molecule of many more
ribonucleotides than that comprising the ultimate functional mRNA. This primary
transcript may range from 500 to 50,000 nucleotides; it remains confined to the
nucleus and is called heterogeneous nuclearRNA(hnRNA). The fate of this
hnRNA may be one of the followings : 1. RNA transcripts of some genes do not
seem to give rise any cytoplasmic mRNA, but get degraded within the nucleus.
The hnRNA molecules which are destined to produce functional mRNA, undergo
RNAprocessing which includes the following steps :
1. Addition of a cap of 7-MeG or m7G. During capping process, a cap of a
methylated guanosine, called 7-methylguanosine (7-MeG or m7G) , is added to 5'
end of primary transcript (i.e., hnRNA) in a rare 5'-5' linkage.
histone proteins.
2. Addition of tail of poly-A. The 3´end of mRNA is generated in two steps
1. Endonuclease enzyme cuts the primary transcript at an appropriate
location.
2. Poly (A) is added to the newly generated end by an enzyme, called poly
(A) polymerase, utilizing ATP as a substrate. This step is called polyadenylation.
3. RNA splicing. This is the controlled excision of large intervening sequences or
introns from the transcript and rejoining of the remaining fragments, called coding
sequences orexons, together
to producethe finished mRNA.
Heterogeneityand types of mRNA.
When the total mRNA population of an organism is considered, it is found to be
heterogeneous in size, showing a wide range of S values of 6 to 30. This property
of mRNA reflects the fact that the size or length of the mRNA molecule is directly
related with the size of the codons for different protein molecules, the sizes of
which may be quite variable.According to the size, the following two
types of mRNA molecules can be recognized.

5. (a) Monocistronic mRNA. Mostly the mRNA carries the codons of single cistron
(i.e., codes for one complete protein molecule) of the DNA. Such mRNA molecule
is called monocistronic
(b) Polygenic or polycistronic mRNA. Sometimes a mRNA molecule carries the
codes from several adjacent DNA cistrons and become much longer in size. This
type of mRNA is called polygenicorpolycistronic mRNA.
(III) TransferRNA (tRNA)
Transfer RNAs (tRNAs) are small RNA molecules containing 75 to 95
nucleotides. Cells contain many different tRNA molecules. Most of the tRNAs
function as carriers of amino acids and participate in protein synthesis.
The RNA which possesses the capacity to combine specifically with only one
amino acid in a reaction mediated by a set of amino acid-specific enzymes, called

6. aminoacyl-tRNA synthetases; transfers that amino acid from the “amino acid
pool” to the site of protein synthesis and recognises the codons of the mRNA is
known as the soluble RNA (sRNA) or transfer RNA (tRNA).
Structure of tRNA. Robert Holley (1965) and his colleagues reported the
complete nucleotide sequence of alanine tRNA of yeast (Holley received the Nobel
Prize in 1968 for his work along with Khorana and Nirenberg). Nucleotide
sequences are now known for more than 100 different “species”of tRNA.
Transfer RNA has several unique characteristics:
1. It is a relatively small molecule of 75 to 90 ribonucleotides and is, thus,
smaller than either mRNA or any of the rRNAs, and has a sedimentation
coefficient of 4S.
2. The ratios of A:U and G:C are near unity which suggests the formation of
DNA-like double helical segments (secondary structure). In these double helical
segments, G:C base pairs are more common than A:U as suggested by the ratio
AU:GC = 0.7
3. All tRNA molecules have a tertiary structure, the details for which are now
known and Mg2+ ion concentration is important for its stabilization.
Three-dimensionalstructure of tRNA.
In order to understand the structure-function relationship of tRNA, its three
dimensional structure (TDS) was worked out by the help of X-ray crystallography
study. A.Klug, the Nobel laureate of 1982, has contributed much to the TDS of
tRNAs. S.H.Kim(1973) proposed a most acceptable TDS model of tRNA (i.e.,
phenyl-alaninetRNA of yeast cells).
Genes for tRNA. There are, probably, at least 30 to 40 different tRNA genes and
tRNA molecules in E.coli. Higher organisms are found to contain 60 tRNA
molecules and 60 tRNA genes. Since the cell uses only 20 amino acids in protein
synthesis (and probably only 20 synthetase enzymes), it follows that several tRNA
will often have an affinity for the same amino acid. For example, E. coli cells
contain five species of tRNA for leucine amino acid.
All the tRNA genes constitute far less than 1% of total genome in both E.coli and
eukaryotic cells, yet some 10 to 15% of each cell’s RNA may be in the form of
tRNA. This discrepancy between the number of tRNA genes and gene transcripts
occurs because of the following facts—(1) The tRNA molecules are relatively
stable compared with many kinds of RNA. (2) The tRNA molecules are
transcribed continuously and more quickly by tRNA genes than other RNAs
because they are needed in plentiful amounts.

7. Biologicalroles ofncRNA
Noncoding RNAs belong to several groups and are involved in many cellular
processes. These range from ncRNAs of central importance that are conserved
across all or most cellular life through to more transient ncRNAs specific to one or
a few closely related species. The more conserved ncRNAs are thought to be
molecular fossils or relics from LUCA and the RNA world and their current roles
remain mostly in regulation of information flow from DNA to protein.
ncRNAs in translation

8. Other functions includencRNAs in RNA splicing
 ncRNAs in DNA replication
 ncRNAs in gene regulation
 The expression of many thousands of genes are regulated by ncRNAs. This
regulation can occurin trans or in cis.
 Trans-acting ncRNAs
 In higher eukaryotes microRNAs regulate gene expression. A single miRNA
can reduce the expression levels of hundreds of genes.
 Cis-acting ncRNAs
ncRNAs and genome defense
Piwi-interacting RNAs (piRNAs) expressed in mammalian testes and somatic cells
form RNA-protein complexes with Piwi proteins. These piRNA complexes
(piRCs) have been linked to transcriptional gene silencing of retrotransposons and
other genetic elements in germ line cells, particularly those in spermatogenesis.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are repeats
found in the DNA of many bacteria and archaea. The repeats are separated by
spacers of similar length. It has been demonstrated that these spacers can be
derived from phage and subsequently help protectthe cell from infection.
ncRNAs and chromosome structure
Telomerase is an RNP enzyme that adds specific DNA sequence repeats
("TTAGGG" in vertebrates) to telomeric regions, which are found at the ends of
eukaryotic chromosomes. The telomeres contain condensed DNA material, giving
stability to the chromosomes. The enzyme is a reverse transcriptase that carries
Telomerase RNA, which is used as a template when it elongates telomeres, which
are shortened after each replication cycle.
Xist (X-inactive-specific transcript) is a long ncRNA gene on the X chromosome
of the placental mammals that acts as major effector of the X chromosome
inactivation process forming Barr bodies. An antisense RNA, Tsix, is a negative
regulator of Xist. X chromosomes lacking Tsix expression (and thus having high
levels of Xist transcription) are inactivated more frequently than normal
chromosomes. In drosophilids, which also use an XY sex-determination system,
the roX (RNA on the X) RNAs are involved in dosage compensation Both Xist and

9. roX operate by epigenetic regulation of transcription through the recruitment of
histone-modifying enzymes.
Bifunctional RNA
Bifunctional RNAs, or dual-function RNAs, are RNAs that have two distinct
functions. The majority of the known bifunctional RNAs are both mRNAs that
encode a protein and ncRNAs. However there are also a growing number of
ncRNAs that fall into two different ncRNA categories; e.g., H/ACA box snoRNA
and miRNA.
Two well known examples of bifunctional RNAs are SgrS RNA and RNAIII.
However, a handful of other bifunctional RNAs are known to exist (e.g., steroid
receptor activator/SRA, VegT RNA, Oskar RNA ENOD40, p53 RNA and SR1
RNA Bifunctional RNAs have recently been the subject of a special issue of
Biochimie.
ncRNAs and disease
As with proteins, mutations or imbalances in the ncRNA repertoire within the body
can cause a variety of diseases.
Cancer
Many ncRNAs show abnormal expression patterns in cancerous tissues. These
include miRNAs long mRNA-like ncRNAs GAS5, SNORD50 telomerase RNA
and Y RNAs. The miRNAs are involved in the large scale regulation of many
protein coding genes, the Y RNAs are important for the initiation of DNA
replication, telomerase RNA that serves as a primer for telomerase, an RNP that
extends telomeric regions at chromosome ends (see telomeres and disease for more
information). The direct function of the long mRNA-like ncRNAs is less clear.
The p53 tumor suppressor is arguably the most important player in preventing
tumor formation and progression. The p53 protein functions as a transcription
factor with a crucial role in orchestrating the cellular stress response. In addition to
its crucial role in cancer, p53 has been implicated in other diseases including
diabetes, cell death after ischemia, and various neurodegenerative diseases such as
Huntington, Parkinson, and Alzheimer. Studies have suggested that p53 expression
is subject to regulation by non-coding RNA.[4]

10. Prader–Willisyndrome
The deletion of the 48 copies of the C/D box snoRNA SNORD116 has been shown
to be the primary cause of Prader–Willi syndrome. Prader–Willi is a
developmental disorder associated with over-eating and learning difficulties.
SNORD116 has potential target sites within a number of protein-coding genes, and
could have a role in regulating alternative splicing.
Alzheimer's disease
The antisense RNA, BACE1-AS is transcribed from the opposite strand to BACE1
and is upregulated in patients with Alzheimer's disease.[71] BACE1-AS regulates
the expression of BACE1 by increasing BACE1 mRNA stability and generating
additional BACE1 through a post-transcriptional feed-forward mechanism. By the
same mechanism it also raises concentrations of beta amyloid, the main constituent
of senile plaques. BACE1-AS concentrations are elevated in subjects with
Alzheimer's disease and in amyloid precursorprotein transgenic mice.
Control of transposable elements
Transposable elements were first discovered in the 1940s (McClintock, 1950) and
are now known to make up a large portion of the genomes of most organisms. For
example, 10% of the Arabidopsis genome consists of transposons and transposon
remains, and transposons account for 45% of the sequence of the human genome.
The ability of transposons to integrate at novel sites in the genome makes them
intrinsically mutagenic and therefore an important silencing target. Early on, the
phenomenon of transposon silencing was found to have substantial genetic overlap
with RNAi in C. elegans (Ketting et al., 1999; Sijen and Plasterk, 2003; Tabara et
al., 1999; Tijsterman et al., 2002; Tops et al., 2005; Vastenhouw et al., 2003).
However, it is still unknown whether transposon silencing in worms happens at a
posttranscriptional or transcriptional level.
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