PMID- 34836959
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20230208
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Nov 26
TI  - Fat mass and obesity-associated protein regulates RNA methylation associated with 
      depression-like behavior in mice.
PG  - 6937
LID - 10.1038/s41467-021-27044-7 [doi]
LID - 6937
AB  - Post-transcriptional modifications of RNA, such as RNA methylation, can 
      epigenetically regulate behavior, for instance learning and memory. However, it 
      is unclear whether RNA methylation plays a critical role in the pathophysiology 
      of major depression disorder (MDD). Here, we report that expression of the fat 
      mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in 
      the hippocampus of patients with MDD and mouse models of depression. Suppressing 
      Fto expression in the mouse hippocampus results in depression-like behaviors in 
      adult mice, whereas overexpression of FTO expression leads to rescue of the 
      depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine 
      (m(6)A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout 
      (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 
      (Adrb2) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like 
      behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly 
      via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest 
      that FTO is a regulator of a mechanism underlying depression-like behavior in 
      mice.
CI  - (c) 2021. The Author(s).
FAU - Liu, Shu
AU  - Liu S
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Xiu, Jianbo
AU  - Xiu J
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Zhu, Caiyun
AU  - Zhu C
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Meng, Kexin
AU  - Meng K
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Li, Chen
AU  - Li C
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Han, Rongrong
AU  - Han R
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Du, Tingfu
AU  - Du T
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Li, Lanlan
AU  - Li L
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Xu, Lingdan
AU  - Xu L
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Liu, Renjie
AU  - Liu R
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Zhu, Wanwan
AU  - Zhu W
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Shen, Yan
AU  - Shen Y
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
FAU - Xu, Qi
AU  - Xu Q
AUID- ORCID: 0000-0003-2660-8092
AD  - State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, 100005, China. qixu@vip.sina.com.
AD  - Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China. 
      qixu@vip.sina.com.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20211126
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (ADRB2 protein, mouse)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - CLE6G00625 (N-methyladenosine)
RN  - EC 1.14.11.- (FTO protein, mouse)
RN  - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
RN  - EC 1.14.11.33 (FTO protein, human)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*analogs & derivatives/metabolism
MH  - Adult
MH  - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics/*metabolism
MH  - Animals
MH  - Case-Control Studies
MH  - Depressive Disorder, Major/blood/*genetics/pathology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Healthy Volunteers
MH  - Hippocampus/pathology
MH  - Humans
MH  - Male
MH  - Methylation
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Receptors, Adrenergic, beta-2/*genetics
MH  - Young Adult
PMC - PMC8626436
COIS- The authors declare no competing interests.
EDAT- 2021/11/28 06:00
MHDA- 2022/01/08 06:00
PMCR- 2021/11/26
CRDT- 2021/11/27 05:38
PHST- 2021/01/31 00:00 [received]
PHST- 2021/10/28 00:00 [accepted]
PHST- 2021/11/27 05:38 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2021/11/26 00:00 [pmc-release]
AID - 10.1038/s41467-021-27044-7 [pii]
AID - 27044 [pii]
AID - 10.1038/s41467-021-27044-7 [doi]
PST - epublish
SO  - Nat Commun. 2021 Nov 26;12(1):6937. doi: 10.1038/s41467-021-27044-7.