Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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NAT10 inhibition improves cellular phenotypes of Hutchinson-Gilford progeria syndrome by restoring the Transportin-1 pathway

ABSTRACT: In this experiment, we aim to examine the role of NAT10 inhibition in Hutchinson-Gilford progeria syndrome (HGPS), a rare but devastating premature ageing syndrome caused by a mutation in the LMNA gene. NAT10 inhibition improves HGPS cellular phenotypes by releasing Transportin-1 (TNPO1) from the cytoplasm, restoring the TNPO1 pathway and allowing hnRNPA1 and NUP153 nuclear import, TPR anchorage at the nuclear pore complexes and RanGTP gradient re-balancing. We have promoted NAT10 inhibition by two ways in normal or patient derived primary skin fibroblasts; the NAT10 inhibitor Remodelin, and an siRNA directly targeting NAT10 (siNAT10). In addition, we have also used an siRNA against TNPO1 and a combined siTNPO1 and siNAT10 treatment. This is a 2-factor design, with treatment (Remodelin vs untreated, or siNAT10 vs siCT) and condition (HGPS vs normal fibroblasts) as the two conditions. Transcriptional profiling was performed using HumanHT-12 v4 Expression BeadChip microarrays, and all conditions were run in triplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Sam Robson

PROVIDER: E-MTAB-6651 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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NAT10 inhibition improves cellular phenotypes of Hutchinson-Gilford progeria syndrome by restoring the Transportin-1 pathway

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