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

Research output: Contribution to journalArticlepeer-review

330 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
Pages (from-to)207-225.e24
JournalCell
Volume184
Issue number1
DOIs
StatePublished - 7 Jan 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

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.

FundersFunder number
Camp4 Therapeutics
Dewpoint Therapeutics
Formal Analysis
Harvard Center for Biomedical Imaging
Harvard Quantitative Biology Initiative
NSF-Simons1764269
Omega Therapeutics
Syros Pharmaceuticals
National Science FoundationPHY-1743900
National Institutes of HealthGM123511, CA155258, 1F32CA254216-01, GM134734
National Institute of General Medical SciencesR01GM034277
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology

    Keywords

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

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