Abstract
Post-transcriptional regulation plays a major role in the generation of cell type diversity. In particular, alternative splicing increases diversification of transcriptome between tissues, in different cell types within a tissue, and even in different compartments of the same cell. The complexity of alternative splicing has increased during evolution. With increasing sophistication, however, comes greater potential for malfunction of these intricate processes. Indeed, recent years have uncovered a wealth of disease-causing mutations affecting RNA-binding proteins and non-coding regions on RNAs, highlighting the importance of studying disease mechanisms that act at the level of RNA processing. For instance, mutations in TARDBP and FUS, or a repeat expansion in the intronic region of the C9ORF72 gene, can all cause amyotrophic lateral sclerosis. We discuss how interspecies differences highlight the necessity for human model systems to complement existing non-human approaches to study neurodegenerative disorders. We conclude by discussing the improvements that could further increase the promise of human pluripotent stem for cell-based disease modeling.
Original language | English |
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Pages (from-to) | 129-138 |
Number of pages | 10 |
Journal | Brain Research |
Volume | 1462 |
DOIs | |
Publication status | Published - 26 Jun 2012 |
Keywords / Materials (for Non-textual outputs)
- REPERFUSION INJURY
- HEXANUCLEOTIDE REPEAT
- MYOTONIC-DYSTROPHY
- EFFICIENT NEURAL CONVERSION
- Neurodegenerative disease
- DIRECTED DIFFERENTIATION
- FUNCTIONAL ORGANIZATION
- Pluripotent stem cell (hPSC)
- SPINAL MUSCULAR-ATROPHY
- AMYOTROPHIC-LATERAL-SCLEROSIS
- HUMAN IPS CELLS
- CORTICOSPINAL TRACT
- RNA-binding protein (RBP)
- Induced pluripotent stem cell (iPSC)
- Embryonic stem cell (ESC)