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 Definition
 History of Ribozyme discovery
 Characteristics of Ribozyme
 Structure and mechanism of Ribozyme
 Types of Ribozymes
 Applications
 Ribozymes (ribonucleic acid enzymes)
are RNA molecules that are capable of catalyzing
specific biochemical reactions, similar to the action of
protein enzymes.
 Discovery revealed that RNA contributed to the ‘RNA
world hypothesis’
 major role
a. Hydrolysis of phosphodiester bonds
b. Formation of bonds
c. Catalyze amino transferase activity of the
ribosome
• 1967 - Carl Woese, Francis Crick, and Leslie Orgel suggested
for the first time that RNA could act as a catalyst.
• 1970, Tomas R.Cech discovered the auto-splicing mechanism
of RNA molecule in Tetrahymena thermophila
• 1980s-T.R. Cech discovered catalytic RNAs
• 1982, Kelly Kruger coined the term ‘Ribozyme’ for these
catalytic RNA and published in “Cell”.
• mid-1980s Sidney Altman unraveled RNase P and its catalytic
role at University of Yale.
• 1989, T.R. Cech and S. Altman shared the Nobel Prize in
chemistry for their contributions in unraveling the catalytic
properties of RNA.
• 2001 "B6.61" could add up to 20 bases to a primer template
 Contrary to central dogma
 associated with metal ions
 Uses RNA as its substrate
 cleave other RNA molecules which
contained the NUX pattern of nucleotides
 Present in every living organism
 follows Michael-Menten kinetics
 diverse structures and mechanisms using the
four nitrogen base choices other than the
diverse amino acids for protein structure
Image showing diversity of ribozyme structure
(Leadzyme, hammer head, twister ribozymes)
• Capable of cleaving mRNA molecules in a sequence specific,
catalytic manner.
• They contain sequences for selective ligation, cleavage reaction
with target mRNAs.
• By modifying substrate recognising sequences , ribozyme can be
specifically tailored for the supression of particular geners
• involved in the
processing of
mRNA, tRNA &
rRNA.
• Splicing requires a
guanine residue
cofactor
• Self splicing by
trans esterification
 known as true RNAzyme
 A ribonucleoprotein, discovered around 40
years ago
 Mechanism of clevage is hydrolysis
 Tiny 30 nucleotide autocatalytic RNA
 It plays a role in reversible cleavage and joining
reactions at very specific site within RNA.
 Hammerhead ribozymes RNAs were discovered initially
in satellite RNAs and viroids (plant viruses.
 hepatitis delta virus (HDV) ribozyme
 85 nucleotide long, non coding
 plays role in viral replication. It is the only known
ribozyme required for the viability of a human
pathogen.
 VS or Varkud satellite ribozyme is the largest
known natural nucleolytic RNA
 satellite RNA is found in mitochondria of some
fungal strains like Neurospora
 small ribozymes found
in RNA satellites of
plant viruses.
 It assists in the
cleavage & ligation of
products of replication
to form circular and
linear satellite RNAs.
 Leadzyme- natural counterparts are in 5SrRNA.
 Ligase ribozyme- catalyse the assembly of RNA
fragments to form its polymer
 Allosteric ribozyme- act as molecular switches
 regulatory segment of a messenger RNA molecule that
binds a small molecule, resulting in a change in
production of the proteins encoded by the mRNA
 e-pathsala
 https://www.annualreviews.org/doi/full/10.1146/annurev.biophys.30.
1.457
 Slideshare.net
 https://www.news-medical.net/life-sciences/What-are-
Ribozymes.aspx
Thank you

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Ribozyme

  • 1.
  • 2.  Definition  History of Ribozyme discovery  Characteristics of Ribozyme  Structure and mechanism of Ribozyme  Types of Ribozymes  Applications
  • 3.  Ribozymes (ribonucleic acid enzymes) are RNA molecules that are capable of catalyzing specific biochemical reactions, similar to the action of protein enzymes.  Discovery revealed that RNA contributed to the ‘RNA world hypothesis’  major role a. Hydrolysis of phosphodiester bonds b. Formation of bonds c. Catalyze amino transferase activity of the ribosome
  • 4. • 1967 - Carl Woese, Francis Crick, and Leslie Orgel suggested for the first time that RNA could act as a catalyst. • 1970, Tomas R.Cech discovered the auto-splicing mechanism of RNA molecule in Tetrahymena thermophila • 1980s-T.R. Cech discovered catalytic RNAs • 1982, Kelly Kruger coined the term ‘Ribozyme’ for these catalytic RNA and published in “Cell”. • mid-1980s Sidney Altman unraveled RNase P and its catalytic role at University of Yale. • 1989, T.R. Cech and S. Altman shared the Nobel Prize in chemistry for their contributions in unraveling the catalytic properties of RNA. • 2001 "B6.61" could add up to 20 bases to a primer template
  • 5.  Contrary to central dogma  associated with metal ions  Uses RNA as its substrate  cleave other RNA molecules which contained the NUX pattern of nucleotides  Present in every living organism  follows Michael-Menten kinetics
  • 6.  diverse structures and mechanisms using the four nitrogen base choices other than the diverse amino acids for protein structure Image showing diversity of ribozyme structure (Leadzyme, hammer head, twister ribozymes)
  • 7. • Capable of cleaving mRNA molecules in a sequence specific, catalytic manner. • They contain sequences for selective ligation, cleavage reaction with target mRNAs. • By modifying substrate recognising sequences , ribozyme can be specifically tailored for the supression of particular geners
  • 8.
  • 9. • involved in the processing of mRNA, tRNA & rRNA. • Splicing requires a guanine residue cofactor • Self splicing by trans esterification
  • 10.
  • 11.  known as true RNAzyme  A ribonucleoprotein, discovered around 40 years ago  Mechanism of clevage is hydrolysis
  • 12.  Tiny 30 nucleotide autocatalytic RNA  It plays a role in reversible cleavage and joining reactions at very specific site within RNA.  Hammerhead ribozymes RNAs were discovered initially in satellite RNAs and viroids (plant viruses.
  • 13.  hepatitis delta virus (HDV) ribozyme  85 nucleotide long, non coding  plays role in viral replication. It is the only known ribozyme required for the viability of a human pathogen.  VS or Varkud satellite ribozyme is the largest known natural nucleolytic RNA  satellite RNA is found in mitochondria of some fungal strains like Neurospora
  • 14.  small ribozymes found in RNA satellites of plant viruses.  It assists in the cleavage & ligation of products of replication to form circular and linear satellite RNAs.
  • 15.
  • 16.  Leadzyme- natural counterparts are in 5SrRNA.  Ligase ribozyme- catalyse the assembly of RNA fragments to form its polymer  Allosteric ribozyme- act as molecular switches  regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the proteins encoded by the mRNA
  • 17.
  • 18.  e-pathsala  https://www.annualreviews.org/doi/full/10.1146/annurev.biophys.30. 1.457  Slideshare.net  https://www.news-medical.net/life-sciences/What-are- Ribozymes.aspx Thank you

Editor's Notes

  1. role in replication as well as in biological catalysis. suggeststhat RNA might be the ancestor of the very first living form. The RNA due to its catalytic nature cancleave / ligate RNA &performs other biochemical reactions like peptide bond synthesis.
  2. in 24 hours.
  3. (where N stands for any nucleotide, U for uracil, and X for adenine, uracil, or cytosine) present in the organelles of eukaryotes (nucleus, mitochondria and chloroplasts), amphibians, prokaryotes, bacteriophages, viroids and in satellite viruses that infect plants
  4. tertiary structure of the ribozyme–substrate complex has been examined using a variety of biochemical, biophysical, genetic, and computational methods. By combining techniques like NMR spectroscopy, X-ray crystallography, (FRET) fluorescence resonance energy transfer revealed the structure of the active site. It was found to be comprised of multiple conserved functional groups
  5. small RNAs of 50–150 nucleotides that perform site-specific self-cleavage larger, more structurally complex ribozymes several hundred nucleotides in length 
  6. Found in bacteria , lower eukaryotes, plants The secondary structure comprised of 9 paired regions (p1-p9)
  7. known as true RNAzyme as it process 5’ Leader sequences of t-RNA i.e. CCA
  8. This is also a metalloribozyme. The hammerhead ribozyme has been well studied as a model system for unraveling the structure and function of RNAs for therapeutic purposes was named for its resemblance of the early secondary structure diagrams to a hammerhead BUT ITS TERTIARY STRUCTURE IS MORE LIKE y SHAPED.
  9. without any available structural data and found as embedded in VS RNA.
  10. Even though these are similar to hammer head ribozyme, these do not require a metal cofactor for the reaction. satellite RNA of - tobacco ringspot virus(sTRSV), chicory yellow mottle virus (sCYMV),arabis mosaic virus (sARMV)
  11. Peptidyl transferase is an aminoacyl transferase which is associated with the formation of peptide bonds between adjacent amino acids during the translation process. It is also the primary enzymatic function of the ribosome. Peptidyl transferase activity is only mediated by ribosomal RNA (rRNA) has been well proven by site directed mutational studies.