Download L16 - sRNA Overview

Lecture 16 – Overview of sRNA Signaling
BIOL 5190/6190 Cellular & Molecular Singal Transduction
Prepared by Bob Locy
Last modified -13F
Introductory
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Brief History of sRNAs
• Bacterial – riboswitches
• Eukaryotes –
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miRNA synthesis & function
• Plant paradigm
• Animal paradigm
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siRNA synthesis & function
• Plant paradigm
• Animal paradigm
Introductory
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Brief History of sRNAs
• lin-4 – C. Elegans in 1993 – turned out to be the first small regulatory RNA to be
discovered in eukaryotes.
• Mutant with developmental defects – Animals look terrible, elogated growth,
larval skin, stop molting, apparently partial larval growth arrest
• Independently, RNA interference (RNAi) was discovered
• RNAi involved in control of viral pathogenesis, and artificial RNAi for study of
gene regulation.
• Ultimately demonstrated that “natural” RNAi was viable regulatory process, and
• The discovery of multiple small regulatory RNAs in eukaryotes, and post
transcriptional gene silencing, translational gene silencing, and transcriptional
gene silencing.
Introductory
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Brief History of sRNAs
• RNAi – Post transcriptional gene silencing.
• Originally discovered in transgenic plants, as antisense knockdown of
transcription
• Led to the discovery of hairpins as RNAi agents
• Ultimately, found natural antisense constructs, and naturally produced hairpins miRNAs
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:
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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 11: Cell Proliferation
siRNAs
• Short (small) Interfering RNAs – siRNAs
• NOT miRNAs, produced by different pathways, have different functions
• ARE dsRNA-produced, are non-coding RNAs with regulatory functions
• PTGS
• TGS
• epigenetics
• Usually does not involve hairpin
• Usually does involve an RNA-dependent RNA polymerase
• May be cut by same RNAse III type proteins, but may be isoforms with miRNA
cutters
• Load into RISC complexes
siRNAs
• Animals
• piRNAs – Piwi-interacting siRNAs
• endo-siRNAs
• Plant
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Repeat-associated siRNA – ra-siRNA
Trans-acting siRNA – ta-siRNA
Phased secondary – siRNA – pha-siRNA
cis natural antisense siRNA - cis-NAT-siRNA
trans natural antisense siRNA - trans-NAT-siRNA
Module 11: miRNA Function – Embryonic Stem Cell miRNA