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Status |
Public on Sep 30, 2012 |
Title |
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (RNA-Seq) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
FUS/TLS and TDP-43 are RNA/DNA-binding proteins integrally involved in amyotrophic lateral sclerosis (ALS) and frontal temporal dementia. FUS/TLS is shown to bind RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU binding motif. A characteristic sawtooth-like binding pattern is identified, supporting co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system is shown to alter levels or splicing of >970 mRNAs, most of which are distinct from the RNAs whose maturation is dependent on TDP-43. Nonetheless, only 55 RNAs are reduced upon depletion of either TDP-43 or FUS/TLS from mouse brain and human neurons differentiated from pluripotent stem cells, including mRNAs transcribed from genes with exceptionally long introns and that encode proteins essential for neuronal integrity. A subset of these is significantly lowered in FUS/TLSR521G and TDP-43G298S mutant fibroblasts and in TDP-43 aggregate-containing motor neurons in sporadic ALS, evidence pointing to a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS.
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Overall design |
RNA-Seq of Fus/Tls in 8 week mouse brain
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Contributor(s) |
Yeo GW, Cleveland DW |
Citation(s) |
23023293 |
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Submission date |
Sep 06, 2012 |
Last update date |
May 15, 2019 |
Contact name |
Gene Yeo |
E-mail(s) |
geneyeo@ucsd.edu
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Organization name |
UCSD
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Street address |
2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (1) |
GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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Samples (18)
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This SubSeries is part of SuperSeries: |
GSE40653 |
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs |
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Relations |
SRA |
SRP015437 |
BioProject |
PRJNA174534 |