Transcriptomics

Dataset Information

0

Knockdown of transactive response DNA-binding protein TDP-43 downregulates histone deacetylase 6


ABSTRACT: TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementias and amyotrophic lateral sclerosis. Besides aggregation of TDP-43, loss of nuclear localization is observed in disease. To identify relevant targets of TDP-43, we performed an expression profiling study. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered upon TDP-43 silencing on mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl-tubulin. Expression of wild-type but neither RNA-binding- nor nuclear-localization-deficient TDP-43 restored HDAC6 expression. Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster also showed HDAC6 mRNA decrease. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, downregulation of HDAC6 reduced aggregate formation and increased cytotoxicity of expanded poly-glutamine ataxin-3 in TDP-43 silenced cells. This was completely restored by co-transfection with HDAC6. In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18632 | GEO | 2009/10/20

SECONDARY ACCESSION(S): PRJNA121403

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2019-01-23 | GSE125424 | GEO
2021-03-15 | PXD023852 | Pride
2020-07-27 | GSE147607 | GEO
2024-03-07 | GSE260737 | GEO
2021-07-01 | GSE133047 | GEO
2012-09-30 | E-GEOD-40649 | biostudies-arrayexpress
2012-09-30 | E-GEOD-40651 | biostudies-arrayexpress
2012-09-30 | E-GEOD-40652 | biostudies-arrayexpress
2023-01-09 | GSE216294 | GEO
2024-09-25 | GSE245303 | GEO