RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin

Roberto Bandiera, Rebecca E. Wagner, Thiago Britto-Borges, Christoph Dieterich, Sabine Dietmann, Susanne Bornelöv () and Michaela Frye ()
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Roberto Bandiera: University of Cambridge
Rebecca E. Wagner: German Cancer Research Center—Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280
Thiago Britto-Borges: University Hospital Heidelberg, German Center for Cardiovascular Research (DZHK), Im Neuenheimer Feld 669
Christoph Dieterich: University Hospital Heidelberg, German Center for Cardiovascular Research (DZHK), Im Neuenheimer Feld 669
Sabine Dietmann: Washington University School of Medicine in St. Louis
Susanne Bornelöv: University of Cambridge
Michaela Frye: German Cancer Research Center—Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Pausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis co-regulated cell cycle and chromosome organization. The reduction in transcription involves impaired splicing and RNA decay, but occurs in the absence of chromatin remodelling at promoters and putative enhancers. Thus, RN7SK is directly required for efficient Pol II transcription of highly transcribed bidirectional gene pairs, and thereby exerts tissue-specific functions, such as maintaining a cycling cell population in the epidermis.

Date: 2021
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DOI: 10.1038/s41467-021-26083-4

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