The mechanism underlying redundant functions of the YTHDF proteins

Zhongyu Zou; Caraline Sepich-Poore; Xiaoming Zhou; Jiangbo Wei; Chuan He

doi:10.1186/s13059-023-02862-8

The mechanism underlying redundant functions of the YTHDF proteins

Genome Biol. 2023 Jan 24;24(1):17. doi: 10.1186/s13059-023-02862-8.

Authors

Zhongyu Zou^{1

2}, Caraline Sepich-Poore^{1

2

3

4}, Xiaoming Zhou⁵, Jiangbo Wei^{1

2}, Chuan He^{6

7

8}

Affiliations

¹ Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
² Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, 60637, USA.
³ Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA.
⁴ University of Chicago Medical Scientist Training Program, Chicago, IL, 60637, USA.
⁵ Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
⁶ Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA. chuanhe@uchicago.edu.
⁷ Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, 60637, USA. chuanhe@uchicago.edu.
⁸ Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA. chuanhe@uchicago.edu.

Abstract

The YTH N⁶-methyladenosine RNA binding proteins (YTHDFs) mediate the functional effects of N⁶-methyladenosine (m⁶A) on RNA. Recently, a report proposed that all YTHDFs work redundantly to facilitate RNA decay, raising questions about the exact functions of individual YTHDFs, especially YTHDF1 and YTHDF2. We show that YTHDF1 and YTHDF2 differ in their low-complexity domains (LCDs) and exhibit different behaviors in condensate formation and subsequent physiological functions. Biologically, we also find that the global stabilization of RNA after depletion of all YTHDFs is driven by increased P-body formation and is not strictly m⁶A dependent.

Keywords: P-body; Translation control; YTHDF1; YTHDF2; YTHDF3; m6A.

Publication types

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

MeSH terms

Humans
RNA* / metabolism
RNA-Binding Proteins* / metabolism

Substances

RNA
RNA-Binding Proteins
YTHDF1 protein, human
YTHDF2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding