Protein-RNA Complexes, ALS and Aging

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Protein-RNA complexes, ALS and aging Jernej Ule, ulelab.info

Transcript of Protein-RNA Complexes, ALS and Aging

Page 1: Protein-RNA Complexes, ALS and Aging

Protein-RNA complexes, ALS and aging

Jernej Ule, ulelab.info

Page 2: Protein-RNA Complexes, ALS and Aging

iCLIP: nucleotide-resolution crosslinking and immunoprecipitation

Konig et al., NSMB, 2010Haberman et al, Gen biol, 2017

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Tollervey et al., Nat Neuro, 2011data at http://icount.biolab.si

TDP-43 regulates splicing via UG repeat sequences

regulated exon

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Splicing of TDP-43-regulated alternative exons in human brain

Tollervey et al., Genome Res, 2013

disease-specific

aging-associated

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Alternative splicing affected by aging and/or disease in human brain

Tollervey et al., Genome Res, 2013

disease-specific

aging-associated

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Analysis of cell-type specific gene expression

Tollervey et al., Genome Res, 2013

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Soreq et al., Cell Rep, 2017

Analysis of cell-type specific gene expression upon aging

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Soreq et al., Cell Rep, 2017

Shifts in regional expression profiles of glia-specific genes upon aging

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Summary

Analysis of splicing changes revealed a common component of aging and neurodegeneration

Dramatic decrease of neuron-specific genes is a hallmark of neurodegeneration (as expected)

Distinct changes in cell type-specific expression profiles are a hallmark of aging

Microglia-specific genes increase, and neuron-specific genes slightly decrease their expression

Astrocyte and oligodendrocyte-specific genes shift their regional expression patterns

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Cell-type specific gene patterns in aging

Mina Ryten, John Hardy,UK Brain Expression Consortium

James Rose, Colin Smith,

University of Edinburg

LilachSoreq

RickiePatani

Chris ShawKCL, London

James Tollervey

Aging & TDP-43 in ALS


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