MicroRNAsBiogenesis, 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

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

mRNA

Ribosome

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

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

DI- DeltaN- NotchSu(H)- suppressor of HairlessE(spl)- enhancer of SplitSens- senseless

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?