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Lecture 16 – Overview of sRNA Signaling

Lecture 16 – Overview of sRNA Signaling. BIOL 5190/6190 Cellular & Molecular Singal Transduction Prepared by Bob Locy Last modified -13F. Introductory. Brief History of sRNAs Bacterial – riboswitches Eukaryotes – miRNA synthesis & function Plant paradigm Animal paradigm

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Lecture 16 – Overview of sRNA Signaling

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  1. Lecture 16 – Overview of sRNA Signaling BIOL 5190/6190 Cellular & Molecular Singal Transduction Prepared by Bob Locy Last modified -13F

  2. Introductory • Brief History of sRNAs • Bacterial – riboswitches • Eukaryotes – • miRNA synthesis & function • Plant paradigm • Animal paradigm • siRNA synthesis & function • Plant paradigm • Animal paradigm

  3. Introductory • 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.

  4. Introductory • 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

  5. Module 04: Animal miRNA biogenesis Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

  6. 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 • MicroRNAregulation of differentiation • Differentiation of cardiac cells • Differentiation of smooth muscle cells • Cell proliferation • Apoptosis • Stress responses. • MicroRNAdysregulation and cancer

  7. Module 11: Cell Proliferation

  8. 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

  9. siRNAs • Animals • piRNAs – Piwi-interacting siRNAs • endo-siRNAs • Plant • 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

  10. Module 11: miRNA Function – Embryonic Stem Cell miRNA

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