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MicroRNAs
Biogenesis, Function and Regulation
Introduction
• MiRNAs are non-coding RNAs found only in eukaryotic cells.
• Small in size with an average length of 22 nucleotides.
• Transcribed by RNA polymerase II from independent genes
  or introns of protein-coding genes
• They play important gene-regulatory roles in both plants and
  animals.
• The first miRNA (lin-4) was discovered in C.elegans in the
  year 1993.
Biogenesis




Source :- The Role of MicroRNAs in Cholesterol Efflux and Hepatic Lipid Metabolism by Kathryn J. Moore, Katey J. Rayner, Yajaira
Su arez, and Carlos Fern andez-Hernando
Functions of miRNAs
  Gene silencing in plants and animals

               Ribosome


   mRNA




Source :- The widespread regulation of microRNA biogenesis, function and decay by Jacek Krol, Inga
Loedige and Witold Filipowicz.
Functions of miRNAs
Tumor suppression and oncogenes-
•    About 50% of the annotated human miRNAs map within fragile
    sites of chromosomes, which are areas of the genome that are
    associated with various human cancers.

• Recent evidence indicates that miRNAs can function as tumour
  suppressors and oncogenes, and they are therefore referred to
  as ‘oncomirs’.

• Gene therapies that use miRNAs might be an effective approach
  to blocking tumour progression. miRNAs such as let-7, which has
  been shown to negatively regulate the Ras oncogenes, and miR-
  15 and miR-16, which negatively regulate BCL2, are promising
  candidates for cancer treatment.
Source :- Oncomirs — microRNAs with a role in cancer by Aurora Esquela-Kerscher and Frank J. Slack
Functions of miRNAs
  Developmental Switches




Source :- microRNA Functions by Natascha Bushati and Stephen M. Cohen
Functions of miRNAs
Thresholding

DI- Delta
N- Notch
Su(H)- suppressor of Hairless
E(spl)- enhancer of Split
Sens- senseless




Source :- MicroRNA-9a ensures the
precise specification of sensory organ
precursors in Drosophila by Yan Li, Fay
Wang, Jin-A Lee, et al.
Regulation of miRNAs
The need :-
• Many miRNAs are expressed in a tissue-specific or developmental
  stage- specific manner, thereby greatly contributing to cell-type-
  specific profiles of protein expression.

• With the potential to target dozens or even hundreds of different
  mRNAs, individual miRNAs can coordinate or fine-tune the
  expression of proteins in a cell.

• These considerations call for a tight and dynamic regulation of
  miRNA levels and activity, particularly during rapid developmental
  transitions or changes in cellular environment.
Regulation of miRNAs
Regulation of transcription
Stimulates expression of miR-34 and miR-107 which enhances
cell cycle arrest and apoptosis

                                      Stimulates expression of oncogenic miRNAs but inhibits
                                      expression of tumor suppressor miRNAs




Source :- The widespread regulation of microRNA biogenesis, function and decay by Jacek Krol, Inga
Loedige and Witold Filipowicz.
Regulation of miRNAs
Regulation of processing




Source :- The widespread regulation of microRNA
biogenesis, function and decay by Jacek Krol, Inga
Loedige and Witold Filipowicz.
Future perspectives
• The past several years have witnessed tremendous
  progress in our understanding of miRNAs.
• Still several important questions remain to be answered.
• Understanding how miRNAs are processed and how
  they are integrated into the complex regulatory networks
  will be crucial.
• Considering the fundamental role of miRNAs in
  organismal development, cellular differentiation and
  metabolism, viral infection, and oncogenesis, we can
  anticipate many more sophisticated mechanisms for the
  regulation of their biogenesis, function and catabolism to
  emerge in coming years.
References
• The widespread regulation of microRNA biogenesis, function and
  decay by Jacek Krol, Inga Loedige and Witold Filipowicz.

• MicroRNA Functions by Natascha Bushati and Stephen M. Cohen.

• MicroRNA-9a ensures the precise specification of sensory organ
  precursors in Drosophila by Yan Li, Fay Wang, Jin-A Lee, et al.

• Oncomirs — microRNAs with a role in cancer by Aurora Esquela-
  Kerscher and Frank J. Slack
Questions?

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miRNA

  • 2. Introduction • MiRNAs are non-coding RNAs found only in eukaryotic cells. • Small in size with an average length of 22 nucleotides. • Transcribed by RNA polymerase II from independent genes or introns of protein-coding genes • They play important gene-regulatory roles in both plants and animals. • The first miRNA (lin-4) was discovered in C.elegans in the year 1993.
  • 3. Biogenesis Source :- The Role of MicroRNAs in Cholesterol Efflux and Hepatic Lipid Metabolism by Kathryn J. Moore, Katey J. Rayner, Yajaira Su arez, and Carlos Fern andez-Hernando
  • 4. Functions of miRNAs Gene silencing in plants and animals Ribosome mRNA Source :- The widespread regulation of microRNA biogenesis, function and decay by Jacek Krol, Inga Loedige and Witold Filipowicz.
  • 5. Functions of miRNAs Tumor suppression and oncogenes- • About 50% of the annotated human miRNAs map within fragile sites of chromosomes, which are areas of the genome that are associated with various human cancers. • Recent evidence indicates that miRNAs can function as tumour suppressors and oncogenes, and they are therefore referred to as ‘oncomirs’. • Gene therapies that use miRNAs might be an effective approach to blocking tumour progression. miRNAs such as let-7, which has been shown to negatively regulate the Ras oncogenes, and miR- 15 and miR-16, which negatively regulate BCL2, are promising candidates for cancer treatment.
  • 6. Source :- Oncomirs — microRNAs with a role in cancer by Aurora Esquela-Kerscher and Frank J. Slack
  • 7. Functions of miRNAs Developmental Switches Source :- microRNA Functions by Natascha Bushati and Stephen M. Cohen
  • 8. Functions of miRNAs Thresholding DI- Delta N- Notch Su(H)- suppressor of Hairless E(spl)- enhancer of Split Sens- senseless Source :- MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila by Yan Li, Fay Wang, Jin-A Lee, et al.
  • 9. Regulation of miRNAs The need :- • Many miRNAs are expressed in a tissue-specific or developmental stage- specific manner, thereby greatly contributing to cell-type- specific profiles of protein expression. • With the potential to target dozens or even hundreds of different mRNAs, individual miRNAs can coordinate or fine-tune the expression of proteins in a cell. • These considerations call for a tight and dynamic regulation of miRNA levels and activity, particularly during rapid developmental transitions or changes in cellular environment.
  • 10. Regulation of miRNAs Regulation of transcription Stimulates expression of miR-34 and miR-107 which enhances cell cycle arrest and apoptosis Stimulates expression of oncogenic miRNAs but inhibits expression of tumor suppressor miRNAs Source :- The widespread regulation of microRNA biogenesis, function and decay by Jacek Krol, Inga Loedige and Witold Filipowicz.
  • 11. Regulation of miRNAs Regulation of processing Source :- The widespread regulation of microRNA biogenesis, function and decay by Jacek Krol, Inga Loedige and Witold Filipowicz.
  • 12. Future perspectives • The past several years have witnessed tremendous progress in our understanding of miRNAs. • Still several important questions remain to be answered. • Understanding how miRNAs are processed and how they are integrated into the complex regulatory networks will be crucial. • Considering the fundamental role of miRNAs in organismal development, cellular differentiation and metabolism, viral infection, and oncogenesis, we can anticipate many more sophisticated mechanisms for the regulation of their biogenesis, function and catabolism to emerge in coming years.
  • 13. References • The widespread regulation of microRNA biogenesis, function and decay by Jacek Krol, Inga Loedige and Witold Filipowicz. • MicroRNA Functions by Natascha Bushati and Stephen M. Cohen. • MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila by Yan Li, Fay Wang, Jin-A Lee, et al. • Oncomirs — microRNAs with a role in cancer by Aurora Esquela- Kerscher and Frank J. Slack