RNA-Mediated Feedback Control of Transcriptional Condensates

Jonathan E. Henninger, Ozgur Oksuz, Krishna Shrinivas, Ido Sagi, Gary LeRoy, Ming M. Zheng, J. Owen Andrews, Alicia V. Zamudio, Charalampos Lazaris, Nancy M. Hannett, Tong Ihn Lee, Phillip A. Sharp, Ibrahim I. Cissé, Arup K. Chakraborty*, Richard A. Young*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

292 Scopus citations

Abstract

During the early steps of transcription initiation, nascent RNAs stimulate transcriptional condensate formation, whereas the burst of RNAs produced during elongation stimulates condensate dissolution.

Original languageEnglish (US)
Pages (from-to)207-225.e24
JournalCell
Volume184
Issue number1
DOIs
StatePublished - Jan 7 2021

Funding

We are grateful to Dora Tang and Ankur Jain for discussions regarding complex coacervates and their regulation by RNA. We also thank Mehdan Kardar and Young lab members for discussions; D. Reinberg, J.M. Calabrese, R. Jaenisch, and I. Cheeseman for reagents; W. Salmon of the W.M. Keck Microscopy Facility; and E. Diel of the Harvard Center for Biomedical Imaging. This work was supported by NIH grants GM123511 (to R.A.Y.), CA155258 (to R.A.Y.), 1F32CA254216-01 (to J.E.H.), and GM134734 (to I.I.C.); NSF grant PHY-1743900 (to A.K.C., R.A.Y., and P.A.S.); by the NSF-Simons Center for Mathematical and Statistical Analysis of Biology at Harvard (Award Number #1764269 ) and the Harvard Quantitative Biology Initiative (to K.S.); and the Gruss-Lipper postdoctoral fellowship and the Rothschild postdoctoral fellowship (to I.S.). We are grateful to Dora Tang and Ankur Jain for discussions regarding complex coacervates and their regulation by RNA. We also thank Mehdan Kardar and Young lab members for discussions; D. Reinberg, J.M. Calabrese, R. Jaenisch, and I. Cheeseman for reagents; W. Salmon of the W.M. Keck Microscopy Facility; and E. Diel of the Harvard Center for Biomedical Imaging. This work was supported by NIH grants GM123511 (to R.A.Y.), CA155258 (to R.A.Y.), 1F32CA254216-01 (to J.E.H.), and GM134734 (to I.I.C.); NSF grant PHY-1743900 (to A.K.C. R.A.Y. and P.A.S.); by the NSF-Simons Center for Mathematical and Statistical Analysis of Biology at Harvard (Award Number #1764269) and the Harvard Quantitative Biology Initiative (to K.S.); and the Gruss-Lipper postdoctoral fellowship and the Rothschild postdoctoral fellowship (to I.S.). Conceptualization, J.E.H. O.O. K.S. T.I.L. P.A.S. A.K.C. and R.A.Y.; Methodology, J.E.H. O.O. K.S. N.M.H. I.S. M.M.Z. J.O.A. A.V.Z. C.L. and A.K.C.; Software, J.E.H. and K.S.; Formal Analysis, J.E.H. O.O. and K.S.; Investigation, J.E.H. O.O. K.S. I.S. M.M.Z. J.O.A. and A.V.Z.; Resources, N.M.H. G.L. I.I.C. A.K.C. and R.A.Y.; Writing – Original Draft, J.E.H. O.O. K.S. A.K.C. and R.A.Y.; Visualization, J.E.H. O.O. and K.S.; Supervision, A.K.C. and R.A.Y.; Funding Acquisition, P.A.S. A.K.C. and R.A.Y. R.A.Y. is a founder and shareholder of Syros Pharmaceuticals, Camp4 Therapeutics, Omega Therapeutics, and Dewpoint Therapeutics. T.I.L. is a shareholder of Syros Pharmaceuticals and a consultant to Camp4 Therapeutics. A.K.C. and P.A.S. are shareholders and consultants to Dewpoint Therapeutics. A.K.C. is a SAB member of Omega Therapeutics. The Whitehead Institute has filed a patent application based on this study.

Keywords

  • RNA
  • complex coacervates
  • enhancer
  • feedback
  • mediator
  • non-equilibrium
  • noncoding RNA
  • phase separation
  • transcription
  • transcriptional condensates

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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