Transcriptomics

Dataset Information

6

Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (microarray)


ABSTRACT: 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. Microarray of Fus/Tls in 8 week mouse brain

ORGANISM(S): Mus musculus  

SUBMITTER: Gene Yeo   Gene W Yeo  Don W Cleveland 

PROVIDER: E-GEOD-40649 | ArrayExpress | 2012-09-30

SECONDARY ACCESSION(S): GSE40649PRJNA174532

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

2012-09-30 | E-GEOD-40653 | ArrayExpress
2012-09-30 | E-GEOD-40651 | ArrayExpress
2012-09-30 | E-GEOD-40652 | ArrayExpress
2011-03-03 | E-GEOD-27218 | ArrayExpress
2011-03-03 | E-GEOD-27371 | ArrayExpress
2016-07-05 | E-GEOD-77703 | ArrayExpress
2016-07-05 | E-GEOD-77699 | ArrayExpress
2016-07-05 | E-GEOD-77700 | ArrayExpress
2016-07-05 | E-GEOD-77702 | ArrayExpress
2016-07-05 | E-GEOD-77704 | ArrayExpress