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Importance of si rna and microrna
1. DEEPAK KUMAR - M.PHARM 1st YEAR (PHARMACOLOGY)
DEPT. OF PHARMACEUTICAL SCIENCES
MAHARSHI DAYANAND UNIVERSITY, ROHTAK
Importance of siRNA and micro RNA
2. Introduction
In "lower organisms" such as plants, fungi and insects, siRNA can not only
regulate the expression of endogenous genes, but is a major factor in innate
immunity, silencing the expression of foreign genetic material such as viruses.
Both siRNA and miRNA regulate gene expression, but do so in different ways.
siRNA is specific to a particular target (gene sequence) whereas miRNA is not
and a single miRNA can potentially regulate the expression of many different
genes. Thus it is possible to regard miRNA as the more "highly evolved"
system, especially as siRNA does not occur in higher animals such as
mammals, which have replaced siRNA with other antiviral mechanisms such
as Interferon.
3.
4. What is siRNA?
Small interfering RNA, sometimes
known as short interfering RNA or
silencing RNA, is a class of double-
stranded RNA molecules, 20-25 base
pairs in length, similar to miRNA,
and operating within the RNA
interference pathway
5. Importance of siRNA
siRNAs are widely used to assess the individual contributions of genes to an
assortment of cellular phenotypes including cytokinesis, apoptosis, insulin signaling
and cell differentiation. siRNA screens have been used to identify novel pathways
and have had significant impact in validating targets for a number of cellular
processes and diseases including cancer, HIV infection and hepatitis. Finally, in vivo
RNAi has been used for target validation studies in animal disease models and has
the potential to be used for therapeutic purposes where disease-causing genes are
selectively targeted and suppressed. When a mammal cell is faced with a double-
stranded RNA such as a siRNA, it may mistake it as a viral by-product and initiate
an immune response. In addition, the introduction of an siRNA may cause
unintended off targeting where other nonthreatening protein may also be attacked
and knocked out.
6. Chemically Modifying siRNAs
• Enhanced activity
• Increased serum stability and less off-targets
• Decreased immunological activation
Many diseases can potentially be treated by inhibiting gene
expression. Therefore, the design of synthetic siRNA for
therapeutic uses has become a popular objective of many
biopharmaceutical companies.
7. What is Micro RNA?
A microRNA (abbreviated miRNA) is a small non-coding RNA molecule
(containing about 22 nucleotides) found in plants, animals and some
viruses, that functions in RNA silencing and post-transcriptional
regulation of gene expression.
MicroRNAs (or miRNAs) comprise a novel class of small, non-
coding endogenous RNAs that regulate gene expression by directing
their target mRNAs for degradation or translational repression. Their
discovery added a new dimension to the understanding of complex
gene regulatory networks in humans and animals alike.
8. MicroRNA discovery
• MicroRNA (miRNA) was initially discovered in Caenorhabditis
elegans by Victor Ambros' laboratory in 1993 while studying the
gene lin14. At the same time, Gary Ravkun identified the first
miRNA target gene. Those two groundbreaking discoveries
identified a novel mechanism of posttranscriptional gene regulation.
• In humans alone over 700 miRNAs have been identified and fully
sequenced, and the estimated number of miRNA genes in a human
genome is more than one thousand. Based on computer models,
miRNAs in humans have a direct influence on at least 30% of the
genes in the whole genome.
9. Importance of microRNA
miRNAs represent small RNA molecules encoded in the
genomes of plants and animals. These highly conserved 22
nucleotides long RNA sequences regulate the expression of
genes by binding to the 3'untranslated regions (3'UTR) of
specific mRNAs. A growing body of evidence shows that
miRNAs are one of the key players in cell differentiation
and growth, mobility and apoptosis (programmed cell
death).
10. Differentiating miRNAs from other classes of small RNAs
that are present in the cell is often cumbersome –
particularly the distinction from endogenous small
interfering RNAs (siRNAs). The most significant
distinction between miRNAs and siRNAs is whether they
silence their own expression. Almost all siRNAs
(regardless of their viral or other origin) silence the same
locus from which they were derived. On the other hand,
most miRNAs do not silence their own loci, but other
genes instead.
11. miRNAs regulate diverse aspects of development and
physiology, thus understanding its biological role is proving
more and more important. Analysis of miRNA expression
may provide valuable information, as dysregulation of its
function can lead to human diseases such as cancer,
cardiovascular and metabolic diseases, liver conditions and
immune dysfunction.
Recent studies showed that amplification or overexpression
of a miRNA that down-regulates a tumor suppressor or
other important genes involved in differentiation might
contribute also to tumor formation by stimulating
proliferation, angiogenesis, and invasion