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Integrator complex subunit 12 is a key regulator of human protein synthesis pathways

ABSTRACT: Genome wide association studies of human lung function have identified a signal on 4q24 but the mechanistic basis for this signal is unclear. This region contains the Integrator Complex subunit 12 gene (INTS12) and nearby polymorphisms associated with lung function correlate with INTS12 expression. We aimed to define INTS12 function in human bronchial epithelial cells. RNAseq pathway analyses of INTS12 depleted cells revealed robust downregulation of several protein synthesis related pathways, including the aminoacyl tRNA synthetases and PERK regulated gene expression. Indeed, INTS12 knockdown using mRNA silencing repressed cellular translation and proliferation. ChIPseq gene-centric analyses revealed INTS12 binding to be near transcriptional start sites. The binding was found to be enriched for differentially expressed loci identifying the genes it regulates, a finding previously unknown for this particular member of Integrator complex. These findings contribute to the biology behind genetic association

ORGANISM(S): Homo sapiens

PROVIDER: GSE80386 | GEO | 2017/06/12

SECONDARY ACCESSION(S): PRJNA318778

REPOSITORIES: GEO

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