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Akerman et al. studied the function of human β cell lncRNAs with RNAi, CRISPRi, and
co-expression networks. This revealed β cell lncRNAs and transcription factors that
control common regulatory networks. One lncRNA, PLUTO, is downregulated in type 2
diabetes and controls PDX1, encoding a key β cell transcription factor.
In this work, the authors used lentiviral vectors carrying amiRNAs targeting TFs and lncRNAs to investigate the function of β cell-specific lncRNAs and transcription factors.
This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. They further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.