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Tricks that our cells use to express their genes in the brain, and how aging affects this
Published on 2017-09-221105 Views
Each RNA in our cells is coated by dozens, if not hundreds of RNA-binding proteins. To understand how these proteins act in our cells, we obtain detailed maps of their RNA binding sites. For this purp
Presentation
Tricks that our cells use to express their genes in the brain, and how aging affects this00:00
How do genes get expressed?63:49:43
How RNA processing affects gene expression? - 193:41:12
How RNA processing affects gene expression? - 2125:41:42
TDP-43: an RNA-binding protein associated with ALD and FTD186:39:58
Mutations in RNA-binding proteins cause many diseases202:25:38
Human induced pluripotent cells (iPSCs) as a disease model227:08:22
RNA remodelling during motor neurogenesis in human iPS models of ALS - 1266:27:06
RNA remodelling during motor neurogenesis in human iPS models of ALS - 2348:32:28
RNA remodelling during motor neurogenesis in human iPS models of ALS - 3360:19:09
Why might RNA processing be modified in ALS? 374:54:49
Each RNA interacts with RNA-binding proteins (RBPs)387:47:41
Dynamics of ribonucleoprotein complexes in development, disease and evolution392:15:37
iCLIP: nucleotide-resolution crosslinking and immunoprecipitation419:26:11
TDP-43 regulates splicing in a position-dependent manner445:12:14
TDP-43 regulates splicing & alternative polyadenylation475:33:28
TDP-43 binding around the regulated polyA sites501:20:41
Comparison of TDP-43 binding in FTLD vs. healthy control brain tissue521:44:15
TDP-43 binds to NEAT1, a long non-coding RNA (lncRNA)530:15:30
Paraspeckles are assembled by NEAT1538:27:48
Protein-RNA complexes often form membraneless organelles550:09:11
Occurrence of NEAT1 ncRNA is increased in ALS motor neurons574:35:03
We studied paraspeckle polyadenylation dynamics during stem cell differentiation584:19:49
NEAT1 and paraspeckles are induced by differentiation603:07:50
TDP-43 represses production of the full NEAT1 transcript611:27:20
TDP-43 binds close to the polyA site in the NEAT1 transcript626:56:49
TDP-43 promotes formation of the short NEAT1 transcript640:10:59
Knockout of the internal polyA site allows production of NEAT1v2648:01:15
Knockdown of TDP-43 allows production of NEAT1v2653:04:06
Paraspeckles partially sequester TDP-43 away from mRNAs662:12:20
Cells overexpressing TDP-43 exhibit a developmental delay677:54:18
Cells lacking NEAT1 exhibit a developmental delay683:59:17
TDPTDP-43 knockdown induces the ‘differentiated’ pattern of 3’ end mRNA processing691:08:20
TDP-43 regulates 3’end processing of SOX2 pre-mRNA703:01:39
TDP-43 is required for expression of SOX2 protein in pluripotent cells716:04:41
Cross-regulation of TDP-43 and paraspeckles promote a bistable switch719:38:20
How are neurodegenerative diseases linked to brain aging?743:54:53
Splicing of TDP-43-regulated alternative exons in human brain766:54:32
Alternative splicing affected by aging and/or disease in human brain802:37:11
Cell types of the brain816:14:00
Changes in cell-type specific gene expression programmes850:10:19
Transcriptional hallmarks of human brain aging862:12:47
Analysis of cell-type specific gene expression upon aging881:33:27
Neuroinflammation in neurodegeneration900:30:35
Immunohistochemistry of NeuN-positive cells in the frontal cortex907:05:37
NeuN-stained image analysis913:15:20
Analysis of astrocyte and oligodendrocyte-specific genes923:20:30
Immunohistochemistry of Olig2-positive cells in the frontal cortex942:52:24
Quantification Olig2-stained images945:21:31
Summary954:07:02
Team978:29:41