Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43

M Polymenidou, C Lagier-Tourenne, KR Hutt… - Nature …, 2011 - nature.com
We used cross-linking and immunoprecipitation coupled with high-throughput sequencing
to identify binding sites in 6,304 genes as the brain RNA targets for TDP-43, an RNA binding …

TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A

AL Brown, OG Wilkins, MJ Keuss, SE Hill, M Zanovello… - Nature, 2022 - nature.com
… To identify novel CEs promoted by TDP-43 depletion, we performed RNA sequencing (RNA-seq)
on human induced pluripotent stem (iPS) cell-derived cortical-like i 3 Neurons, in which …

Characterizing the RNA targets and position-dependent splicing regulation by TDP-43

JR Tollervey, T Curk, B Rogelj, M Briese… - Nature …, 2011 - nature.com
… the RNAs that were bound by TDP-43 in healthy brain tissue and that from subjects with
FTLD with TDP-43 inclusions (FTLD-TDP). Although this was the first study of protein-RNA

Loss of nuclear TDP43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in …

JR Highley, J Kirby, JA Jansweijer… - Neuropathology and …, 2014 - Wiley Online Library
… Loss of nuclear TDP43 characterizes sporadic and most familial forms … TDP43 (encoded
by TARDBP ) has multiple roles in RNA processing. We aimed to determine whether (1) RNA

Mis-spliced transcripts generate de novo proteins in TDP-43–related ALS/FTD

S Seddighi, YA Qi, AL Brown, OG Wilkins… - Science translational …, 2024 - science.org
… identify de novo cryptic peptides caused by RNA mis-splicing in TDP-43-depleted human
iPSC-derived neurons. (B) Proteogenomic analysis of TDP-43-depleted human iPSC-derived …

RNA mis-splicing in disease

MM Scotti, MS Swanson - Nature Reviews Genetics, 2016 - nature.com
… of a vast RNA population that … Indeed, RNA mis-splicing underlies a growing number of
human diseases with substantial societal consequences. Here, we provide an overview of RNA

Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43

PJ Lukavsky, D Daujotyte, JR Tollervey, J Ule… - Nature structural & …, 2013 - nature.com
… how TDP-43 recognizes UG repeats but also how RNA binding–dependent inter-RRM
interactions are crucial for TDP-43 … To assess how TDP-43 recognizes long single-stranded RNA

Quantitative analysis of cryptic splicing associated with TDP-43 depletion

J Humphrey, W Emmett, P Fratta, AM Isaacs… - BMC medical …, 2017 - Springer
RNA-binding proteins in cryptic splicing: TDP-43 and FUS. We analyzed publicly available
TDP-43 depletion RNA… 1–6 in Table 2), FUS depletion RNA-Seq datasets (1 human, 1 murine…

Regulatory role of RNA chaperone TDP-43 for RNA misfolding and repeat-associated translation in SCA31

T Ishiguro, N Sato, M Ueyama, N Fujikake, C Sellier… - Neuron, 2017 - cell.com
… 3B and 3C), indicating that the RNA-binding ability of TDP-43 is essential for its suppression
of UGGAA exp -mediated toxicity. Expression of the TDP-43 RRM mutant did not cause eye …

ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43

ES Arnold, SC Ling, SC Huelga… - Proceedings of the …, 2013 - National Acad Sciences
… of-function by the TDP-43 mutants for individual RNA substrates, from which we conclude
that ALS-linked mutations confer both loss- and gain-of-function properties to TDP-43, and that …