RNA Interferrance

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RNA Interferrance
CMB-234Molecular Biology
Atta ur Rahman school of biological
Science National University of Sciences
Technology
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RNA Interference

• RNA interference (RNAi) is a biological process
  in which RNA molecules inhibit gene expression,
  typically by causing the destruction of
  specific mRNA molecules
•  In 2006, Andrew Fire and Craig C. Mello shared
  the Nobel Prize in Physiology or Medicine for
  their work on RNA interference in
  the nematode worm C. elegans, which they
  published in 1998

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• Interference can be at
• Transcriptional gene silencing (TGS)
• Post transcriptional gene silencing (PTGS)
• Co - transcriptional gene silencing (CTGS)
• Chromatin dependent gene silencing (CDGS)

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Contd

• Three types include
• Micro RNA (21 25nt)
• Small interfering RNA (21 25nt)
• PIWI interacting RNA (24 31nt)

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Generation of RNAi
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siRNA
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miRNA
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piRNA
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RNA Silencing Pathways
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siRNA
Argonaut - PIWI - PAZ - MID
This process can take place here as well RISC
RITS
RISC
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miRNA
Argonaut - PIWI - PAZ - MID
May be present in here
RISC
Translational inhibition
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piRNA
Mechanism of action of pi RNA is not yet fully
elucidated but it is known that it involves the
slicer activity of PIWI Clade It is responsible
for controlling the movement of transposons in
the genome
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Biological Functions
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Linking heterochromatin to RNAi
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Cont

• Gene regulation
• RNA sequences (siRNA and miRNA) that are
  complementary to parts of a promoter can increase
  gene transcription, a phenomenon dubbed RNA
  activation.
• Part of the mechanism for how these RNA
  upregulate genes is known dicer and argonaute are
  involved, possibly via histone demethylation.
• miRNAs have also been proposed to upregulate
  their target genes upon cell cycle arrest,
  although the underlying mechanisms have not been
  elucidated.

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RNAi in DNA Chromatin regulation
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Cont

• Gene Down regulation
• Endogenously expressed miRNAs, are most important
  in translational repression and in the regulation
  of development, especially on the timing
  of morphogenesis and the maintenance
  of undifferentiated or incompletely
  differentiated cell types such as stem cells

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Cont

• In Fission yeast some ciliates, loss of
  heterochromatin gene silencing by del in
• Argonaute (Ago1)
• Dicer (dcr1)
• RNA dependent RNA polymerase (rdp1)
• In Arabidopsis thaliana, RNA directed DNA
  methylation (H3K9)requires 2 proteins
• Dicer (DLC-3)
• Argonaute (AGO-4)
• In Drosophila melanogaster, repeat induced gene
  silencing by
• Polycomb group of genes (PcG)
• PIWI
• DCR-1

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Immune response

• RNA interference is a vital part of the immune
  response to
•  Viruses and
• Other foreign genetic material, especially in
  plants where it may also prevent the
  self-propagation of transposons.

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Future Prospects

• Most mechanisms still unknown
• In future we can employ this mechanism to up or
  down regulate a gene, or to fight viral infections

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Reference
Small RNAs in transcriptional gene silencing and
genome defence Danesh Moazed Nature 457, 413-420
Thank you!