PMID- 32267835
OWN - NLM
STAT- MEDLINE
DCOM- 20200727
LR  - 20210806
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 18
IP  - 4
DP  - 2020 Apr
TI  - YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators.
PG  - e3000664
LID - 10.1371/journal.pbio.3000664 [doi]
LID - e3000664
AB  - The N6-methyladenosine (m6A) modification regulates mRNA stability and 
      translation. Here, we show that transcriptomic m6A modification can be dynamic 
      and the m6A reader protein YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) 
      promotes mRNA decay during cell cycle. Depletion of YTHDF2 in HeLa cells leads to 
      the delay of mitotic entry due to overaccumulation of negative regulators of cell 
      cycle such as Wee1-like protein kinase (WEE1). We demonstrate that WEE1 
      transcripts contain m6A modification, which promotes their decay through YTHDF2. 
      Moreover, we found that YTHDF2 protein stability is dependent on cyclin-dependent 
      kinase 1 (CDK1) activity. Thus, CDK1, YTHDF2, and WEE1 form a feedforward 
      regulatory loop to promote mitotic entry. We further identified Cullin 1 (CUL1), 
      Cullin 4A (CUL4A), damaged DNA-binding protein 1 (DDB1), and S-phase 
      kinase-associated protein 2 (SKP2) as components of E3 ubiquitin ligase complexes 
      that mediate YTHDF2 proteolysis. Our study provides insights into how cell cycle 
      mediators modulate transcriptomic m6A modification, which in turn regulates the 
      cell cycle.
FAU - Fei, Qili
AU  - Fei Q
AUID- ORCID: 0000-0002-0860-2175
AD  - Department of Chemistry, The University of Chicago, Chicago, Illinois, United 
      States of America.
AD  - Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, 
      United States of America.
AD  - Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory 
      of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, 
      Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China.
FAU - Zou, Zhongyu
AU  - Zou Z
AD  - Department of Chemistry, The University of Chicago, Chicago, Illinois, United 
      States of America.
AD  - Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, 
      United States of America.
FAU - Roundtree, Ian A
AU  - Roundtree IA
AD  - Department of Chemistry, The University of Chicago, Chicago, Illinois, United 
      States of America.
AD  - Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, 
      United States of America.
AD  - Medical Scientist Training Program, The University of Chicago, Chicago, Illinois, 
      United States of America.
AD  - Department of Biochemistry and Molecular Biology, The University of Chicago, 
      Chicago, Illinois, United States of America.
AD  - Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, 
      United States of America.
FAU - Sun, Hui-Lung
AU  - Sun HL
AUID- ORCID: 0000-0003-2273-311X
AD  - Department of Chemistry, The University of Chicago, Chicago, Illinois, United 
      States of America.
AD  - Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, 
      United States of America.
FAU - He, Chuan
AU  - He C
AD  - Department of Chemistry, The University of Chicago, Chicago, Illinois, United 
      States of America.
AD  - Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, 
      United States of America.
AD  - Department of Biochemistry and Molecular Biology, The University of Chicago, 
      Chicago, Illinois, United States of America.
AD  - Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, 
      United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200408
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cullin 1)
RN  - 0 (Cullin Proteins)
RN  - 0 (DDB1 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 0 (SKP2 protein, human)
RN  - 0 (YTHDF2 protein, human)
RN  - CLE6G00625 (N-methyladenosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (WEE1 protein, human)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 2.7.11.22 (CDK1 protein, human)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*analogs & derivatives/genetics/metabolism
MH  - CDC2 Protein Kinase/metabolism
MH  - Cell Cycle/*physiology
MH  - Cell Cycle Proteins/genetics
MH  - Cullin Proteins/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Mitosis/*physiology
MH  - Protein Stability
MH  - Protein-Tyrosine Kinases/genetics
MH  - RNA Stability
MH  - RNA-Binding Proteins/genetics/*metabolism
MH  - S-Phase Kinase-Associated Proteins/metabolism
PMC - PMC7170294
COIS- I have read the journal's policy and the authors of this manuscript have the 
      following competing interests: C.H. is a scientific founder of Accent 
      Therapeutics, Inc. and a member of its scientific advisory board.
EDAT- 2020/04/09 06:00
MHDA- 2020/07/28 06:00
PMCR- 2020/04/08
CRDT- 2020/04/09 06:00
PHST- 2019/09/30 00:00 [received]
PHST- 2020/03/20 00:00 [accepted]
PHST- 2020/04/20 00:00 [revised]
PHST- 2020/04/09 06:00 [pubmed]
PHST- 2020/07/28 06:00 [medline]
PHST- 2020/04/09 06:00 [entrez]
PHST- 2020/04/08 00:00 [pmc-release]
AID - PBIOLOGY-D-19-02876 [pii]
AID - 10.1371/journal.pbio.3000664 [doi]
PST - epublish
SO  - PLoS Biol. 2020 Apr 8;18(4):e3000664. doi: 10.1371/journal.pbio.3000664. 
      eCollection 2020 Apr.