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Regulatory features of 5’
nuclear mRNA
Presented By:
Inchara R
9th Semester
Molecular Biology
22/01/2022
Guided By:
Cletus D’Souza
Emeritus Professor
Dept. of Biochemistry
University of Mysore
22/01/2022 Regulatory features of 5’ nuclear mRNA 1
CONTENTS
Introduction
Regulation of translation
• Ferritin Regulation
• Gcn4 Regulation
Conclusion
References
Acknowledgement
22/01/2022 Regulatory features of 5’ nuclear mRNA 2
INTRODUCTION
22/01/2022 Regulatory features of 5’ nuclear mRNA 3
INITITAION:
22/01/2022 Regulatory features of 5’ nuclear mRNA 4
FIG 01: Translation initiation in Eukaryotes
ELONGATION:
22/01/2022 Regulatory features of 5’ nuclear mRNA 5
FIG 02: Steps of translation elongation
TERMINATION:
22/01/2022 Regulatory features of 5’ nuclear mRNA 6
22/01/2022 Regulatory features of 5’ nuclear mRNA 7
FIG 03: Eukaryotic translation termination and ribosome recycling
REGULATION OF TRANSLATION
• Stability and translation of mRNA can be regulated by 5’ and 3’ UTR
of mRNA.
Example is Ferritin Receptor mRNAs
22/01/2022 Regulatory features of 5’ nuclear mRNA 8
An Iron-Regulated, RNA-Binding Protein
Controls Translation of Ferritin
22/01/2022 Regulatory features of 5’ nuclear mRNA 9
FIG 04: Regulation of Ferritin translation by Iron
22/01/2022 Regulatory features of 5’ nuclear mRNA 10
FIG 05: Regulation of the expression of ferritin receptor
Translation of the Yeast Transcriptional
Activator Gcn4
22/01/2022 Regulatory features of 5’ nuclear mRNA 11
FIG 06: Gcn4 mRNA
• After translating uORF1, ribosomes can re-initiate at uORF2 (~50%)
22/01/2022 Regulatory features of 5’ nuclear mRNA 12
FIG 07: Translational control of Gcn4 in response to amino acid starvation
(a) When amino acids are abundant
22/01/2022 Regulatory features of 5’ nuclear mRNA 13
FIG 07: (b) under starvation conditions
Control of translation by eIF2 phosphorylation
22/01/2022 Regulatory features of 5’ nuclear mRNA 14
FIG 07: Reaction stimulated by Amino acid deprivation
CONCLUSION
SOME UNRESOLVED ISSUES
• A critical but poorly understood feature of GCN4 translational control
is the highly disparate capacities of uORF1 and uORF4 to permit
resumption of scanning following translation termination.
• It is also important to understand the molecular basis for activation of
Gcn2p by diverse starvation or stress conditions in amino acid-replete
cells.
22/01/2022 Regulatory features of 5’ nuclear mRNA 15
REFERENCES
• Mathews M.B., Sonenberg N., and Hershey J.W.B. 2007. Translational control in biology and
medicine. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 999pp.
• Robert F. Weaver. 2002. Molecular Biology, 5th Edition, the McGraw-Hill Companies, New York,
914pp.
• Watson, J. D., T. A. Baker, S. P. Bell, A. Gann, M. Levine, R. Losick. 2004. Molecular Biology of
the Gene. 5th Edition. Pearson Education Pte. Ltd., New Delhi, India, 911pp.
• Hinnebusch, A. G. (1997). Translational Regulation of YeastGCN4. Journal of Biological
Chemistry, 272(35), 21661–21664. https://doi.org/10.1074/jbc.272.35.21661
• Hinnebusch, A. G. (2005). Translational regulation of gcn4 and the general amino acid control of
yeast. Annual Review of Microbiology, 59(1), 407–450.
https://doi.org/10.1146/annurev.micro.59.031805.133833
• Gebauer, F., Hentze, M. (2004). Molecular mechanisms of translational control. Nat Rev Mol Cell
Biol 5, 827–835. https://doi.org/10.1038/nrm1488
• Janssen, B. D., & Hayes, C. S. (2012). The tmRNA ribosome-rescue system. Advances in protein
chemistry and structural biology, 86, 151–191.
https://doi.org/10.1016/B978-0-12-386497-0.00005-0
22/01/2022 Regulatory features of 5’ nuclear mRNA 16
• Balvay, L., Soto Rifo, R., Ricci, E. P., Decimo, D., & Ohlmann, T. (2009). Structural and functional
diversity of viral IRESes. Biochimica et biophysica acta, 1789(9-10), 542–557.
https://doi.org/10.1016/j.bbagrm.2009.07.005
• Dever, T. E., & Green, R. (2012). The elongation, termination, and recycling phases of translation in
eukaryotes. Cold Spring Harbor perspectives in biology, 4(7), a013706.
https://doi.org/10.1101/cshperspect.a013706
• Hernández G. (2008). Was the initiation of translation in early eukaryotes IRES-driven?. Trends in
biochemical sciences, 33(2), 58–64. https://doi.org/10.1016/j.tibs.2007.11.002
• Laursen, B. S., Sørensen, H. P., Mortensen, K. K., & Sperling-Petersen, H. U. (2005). Initiation of
protein synthesis in bacteria. Microbiology and molecular biology reviews : MMBR, 69(1), 101–123.
https://doi.org/10.1128/MMBR.69.1.101-123.2005
• Nilsson, J., & Nissen, P. (2005). Elongation factors on the ribosome. Current opinion in structural
biology, 15(3), 349–354. https://doi.org/10.1016/j.sbi.2005.05.004
• Nissen, P., Kjeldgaard, M., & Nyborg, J. (2000). Macromolecular mimicry. The EMBO
journal, 19(4), 489–495. https://doi.org/10.1093/emboj/19.4.489
• Sonenberg, N., & Hinnebusch, A. G. (2009). Regulation of translation initiation in eukaryotes:
mechanisms and biological targets. Cell, 136(4), 731–745. https://doi.org/10.1016/j.cell.2009.01.042
• Weinger, J. S., Parnell, K. M., Dorner, S., Green, R., & Strobel, S. A. (2004). Substrate-assisted
catalysis of peptide bond formation by the ribosome. Nature structural & molecular biology, 11(11),
1101–1106. https://doi.org/10.1038/nsmb841
22/01/2022 Regulatory features of 5’ nuclear mRNA 17
ACKNOWLEDGEMENT
I would like to thank the dept. of Molecular Biology for
providing this opportunity to present this seminar.
I would also like to thank my guide Prof. Cletus D’Souza
for his valuable guidance.
Thank you one and all.
22/01/2022 Regulatory features of 5’ nuclear mRNA 18

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Regulatory features of 5’ nuclear mRNA

  • 1. Regulatory features of 5’ nuclear mRNA Presented By: Inchara R 9th Semester Molecular Biology 22/01/2022 Guided By: Cletus D’Souza Emeritus Professor Dept. of Biochemistry University of Mysore 22/01/2022 Regulatory features of 5’ nuclear mRNA 1
  • 2. CONTENTS Introduction Regulation of translation • Ferritin Regulation • Gcn4 Regulation Conclusion References Acknowledgement 22/01/2022 Regulatory features of 5’ nuclear mRNA 2
  • 4. INITITAION: 22/01/2022 Regulatory features of 5’ nuclear mRNA 4 FIG 01: Translation initiation in Eukaryotes
  • 5. ELONGATION: 22/01/2022 Regulatory features of 5’ nuclear mRNA 5 FIG 02: Steps of translation elongation
  • 7. 22/01/2022 Regulatory features of 5’ nuclear mRNA 7 FIG 03: Eukaryotic translation termination and ribosome recycling
  • 8. REGULATION OF TRANSLATION • Stability and translation of mRNA can be regulated by 5’ and 3’ UTR of mRNA. Example is Ferritin Receptor mRNAs 22/01/2022 Regulatory features of 5’ nuclear mRNA 8
  • 9. An Iron-Regulated, RNA-Binding Protein Controls Translation of Ferritin 22/01/2022 Regulatory features of 5’ nuclear mRNA 9 FIG 04: Regulation of Ferritin translation by Iron
  • 10. 22/01/2022 Regulatory features of 5’ nuclear mRNA 10 FIG 05: Regulation of the expression of ferritin receptor
  • 11. Translation of the Yeast Transcriptional Activator Gcn4 22/01/2022 Regulatory features of 5’ nuclear mRNA 11 FIG 06: Gcn4 mRNA • After translating uORF1, ribosomes can re-initiate at uORF2 (~50%)
  • 12. 22/01/2022 Regulatory features of 5’ nuclear mRNA 12 FIG 07: Translational control of Gcn4 in response to amino acid starvation (a) When amino acids are abundant
  • 13. 22/01/2022 Regulatory features of 5’ nuclear mRNA 13 FIG 07: (b) under starvation conditions
  • 14. Control of translation by eIF2 phosphorylation 22/01/2022 Regulatory features of 5’ nuclear mRNA 14 FIG 07: Reaction stimulated by Amino acid deprivation
  • 15. CONCLUSION SOME UNRESOLVED ISSUES • A critical but poorly understood feature of GCN4 translational control is the highly disparate capacities of uORF1 and uORF4 to permit resumption of scanning following translation termination. • It is also important to understand the molecular basis for activation of Gcn2p by diverse starvation or stress conditions in amino acid-replete cells. 22/01/2022 Regulatory features of 5’ nuclear mRNA 15
  • 16. REFERENCES • Mathews M.B., Sonenberg N., and Hershey J.W.B. 2007. Translational control in biology and medicine. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 999pp. • Robert F. Weaver. 2002. Molecular Biology, 5th Edition, the McGraw-Hill Companies, New York, 914pp. • Watson, J. D., T. A. Baker, S. P. Bell, A. Gann, M. Levine, R. Losick. 2004. Molecular Biology of the Gene. 5th Edition. Pearson Education Pte. Ltd., New Delhi, India, 911pp. • Hinnebusch, A. G. (1997). Translational Regulation of YeastGCN4. Journal of Biological Chemistry, 272(35), 21661–21664. https://doi.org/10.1074/jbc.272.35.21661 • Hinnebusch, A. G. (2005). Translational regulation of gcn4 and the general amino acid control of yeast. Annual Review of Microbiology, 59(1), 407–450. https://doi.org/10.1146/annurev.micro.59.031805.133833 • Gebauer, F., Hentze, M. (2004). Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 5, 827–835. https://doi.org/10.1038/nrm1488 • Janssen, B. D., & Hayes, C. S. (2012). The tmRNA ribosome-rescue system. Advances in protein chemistry and structural biology, 86, 151–191. https://doi.org/10.1016/B978-0-12-386497-0.00005-0 22/01/2022 Regulatory features of 5’ nuclear mRNA 16
  • 17. • Balvay, L., Soto Rifo, R., Ricci, E. P., Decimo, D., & Ohlmann, T. (2009). Structural and functional diversity of viral IRESes. Biochimica et biophysica acta, 1789(9-10), 542–557. https://doi.org/10.1016/j.bbagrm.2009.07.005 • Dever, T. E., & Green, R. (2012). The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harbor perspectives in biology, 4(7), a013706. https://doi.org/10.1101/cshperspect.a013706 • Hernández G. (2008). Was the initiation of translation in early eukaryotes IRES-driven?. Trends in biochemical sciences, 33(2), 58–64. https://doi.org/10.1016/j.tibs.2007.11.002 • Laursen, B. S., Sørensen, H. P., Mortensen, K. K., & Sperling-Petersen, H. U. (2005). Initiation of protein synthesis in bacteria. Microbiology and molecular biology reviews : MMBR, 69(1), 101–123. https://doi.org/10.1128/MMBR.69.1.101-123.2005 • Nilsson, J., & Nissen, P. (2005). Elongation factors on the ribosome. Current opinion in structural biology, 15(3), 349–354. https://doi.org/10.1016/j.sbi.2005.05.004 • Nissen, P., Kjeldgaard, M., & Nyborg, J. (2000). Macromolecular mimicry. The EMBO journal, 19(4), 489–495. https://doi.org/10.1093/emboj/19.4.489 • Sonenberg, N., & Hinnebusch, A. G. (2009). Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell, 136(4), 731–745. https://doi.org/10.1016/j.cell.2009.01.042 • Weinger, J. S., Parnell, K. M., Dorner, S., Green, R., & Strobel, S. A. (2004). Substrate-assisted catalysis of peptide bond formation by the ribosome. Nature structural & molecular biology, 11(11), 1101–1106. https://doi.org/10.1038/nsmb841 22/01/2022 Regulatory features of 5’ nuclear mRNA 17
  • 18. ACKNOWLEDGEMENT I would like to thank the dept. of Molecular Biology for providing this opportunity to present this seminar. I would also like to thank my guide Prof. Cletus D’Souza for his valuable guidance. Thank you one and all. 22/01/2022 Regulatory features of 5’ nuclear mRNA 18