Transcription factors interact with RNA to regulate genes

Ozgur Oksuz; Jonathan E Henninger; Robert Warneford-Thomson; Ming M Zheng; Hailey Erb; Adrienne Vancura; Kalon J Overholt; Susana Wilson Hawken; Salman F Banani; Richard Lauman; Lauren N Reich; Anne L Robertson; Nancy M Hannett; Tong I Lee; Leonard I Zon; Roberto Bonasio; Richard A Young

doi:10.1016/j.molcel.2023.06.012

Transcription factors interact with RNA to regulate genes

Mol Cell. 2023 Jul 20;83(14):2449-2463.e13. doi: 10.1016/j.molcel.2023.06.012. Epub 2023 Jul 3.

Authors

Ozgur Oksuz¹, Jonathan E Henninger¹, Robert Warneford-Thomson², Ming M Zheng³, Hailey Erb¹, Adrienne Vancura¹, Kalon J Overholt⁴, Susana Wilson Hawken⁵, Salman F Banani⁶, Richard Lauman², Lauren N Reich², Anne L Robertson⁷, Nancy M Hannett¹, Tong I Lee¹, Leonard I Zon⁸, Roberto Bonasio², Richard A Young⁹

Affiliations

¹ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
² Epigenetics Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
³ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁵ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Program of Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁶ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁷ Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
⁸ Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA; Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA 02138, USA.
⁹ Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: young@wi.mit.edu.

Abstract

Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function.

Keywords: RNA; RNA-binding proteins; arginine-rich motif; chromatin; development; gene regulation; single-molecule imaging; transcription factor; zebrafish.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Binding Sites
DNA / genetics
Protein Binding
RNA* / metabolism
Transcription Factors* / metabolism

Substances

Transcription Factors
RNA
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding