TY - JOUR
T1 - RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin
AU - Bandiera, Roberto
AU - Wagner, Rebecca E.
AU - Britto-Borges, Thiago
AU - Dieterich, Christoph
AU - Dietmann, Sabine
AU - Bornelöv, Susanne
AU - Frye, Michaela
N1 - Funding Information:
We thank everybody who provided us with reagents. In particular, we thank Arndt G. Benecke and Sebastian Eilebrecht for providing the RN7SK plasmid. We gratefully acknowledge the support of all the Wellcome MRC Cambridge Stem Cell Institute core facility managers, in particular Maike Paramor, Bill Mansfield, Gemini Chu, Peter Humphreys, and Andy Riddell. We also thank John Brown for his help obtaining tissue samples. This work was funded by Cancer Research UK (CR-UK), Worldwide Cancer Research, the Medical Research Council (MRC), the European Research Council (ERC), and the Helmholtz Association. For this research, Michaela Frye’s laboratory was also supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Cambridge Stem Cell Institute. Some parts of figure panels are created with BioRender.com
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85116447976&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-26083-4
DO - 10.1038/s41467-021-26083-4
M3 - Article
C2 - 34620876
AN - SCOPUS:85116447976
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5864
ER -