Lecture 17 – miRNAs in Plants & Animals

BIOL 5190/6190 Cellular & Molecular Singal TransductionPrepared by Bob Locy

Last modified -13F

Introductory

• miRNA synthesis & function• Plant paradigm• Animal paradigm

• siRNA synthesis & function• Plant paradigm• Animal paradigm

Module 11: Cell Proliferation

Module 04: Animal miRNA biogenesis

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

Animal miRNA Function - Overview

The task of establishing microRNA properties and function of individual miRs is ongoing and already there are indications that each miR can modulate the activity of up to 100 mRNAs to influence a large number of key biological processes:

• Maintenance of embryonic stem (ES) cell pluripotency.• MicroRNA modulation of cell-cycle regulatory mechanisms• p53 functions and microRNAs• MicroRNA regulation of differentiation

• Differentiation of cardiac cells• Differentiation of smooth muscle cells

• Cell proliferation• Apoptosis• Stress responses.• MicroRNA dysregulation and cancer

Module 04: Animal miRNA biogenesis

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

Module 04: miRNAs and p53

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

Module 08: Cardiac Development

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

Module 08: Smooth Muscle Cell Differentiation

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

miRNAs in Cancer

• The roles of p53-regulated miR-200c in EMT and stem-cell-like properties. p53 directly binds to the miR-200c promoter and activates its expression. The elevated miR-200c hinders EMT via ZEB1 and reduces cell populations with stem-cell-like properties by BMI1. These pathways prevent the formation of metastatic cancer cells.

• Chen et al. Journal of Biomedical Science 2012 19:90 doi:10.1186/1423-0127-19-90

miRNAs in Cancer

miRNAs & Cancer

• Canonical biogenesis pathway and mechanisms of miRNA deregulation. After RNA polymerse II-dependent transcription, pre-miRNAs are generated from pri-miRNAs or spliced RNA by Drosha-DGCR8 complex or intron splicing pathway, respectively. After exporting to cytoplasm, Dicer digests the pre-miRNAs to the mature miRNAs which guide the miRISC to inhibit target mRNAs. Factors in the yellow box indicate protein regulators or mechanisms leading to the aberrant biogenesis of miRNAs in cancer. See text for more detailed description.

The role of plant hormones in regulating the interaction between biotic and abiotic stress.

Atkinson N J , and Urwin P E J. Exp. Bot. 2012;jxb.ers100

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