PMID- 33731683
OWN - NLM
STAT- MEDLINE
DCOM- 20211005
LR  - 20211005
IS  - 2041-4889 (Electronic)
VI  - 12
IP  - 4
DP  - 2021 Mar 17
TI  - RNA decay in processing bodies is indispensable for adipogenesis.
PG  - 285
LID - 10.1038/s41419-021-03537-7 [doi]
LID - 285
AB  - The RNA decay pathway plays key regulatory roles in cell identities and 
      differentiation processes. Although adipogenesis is transcriptionally and 
      epigenetically regulated and has been thoroughly investigated, how RNA metabolism 
      that contributes to the stability of phenotype-shaping transcriptomes 
      participates in differentiation remains elusive. In this study, we investigated 
      Ddx6, an essential component of processing bodies (PBs) that executes RNA decay 
      and translational repression in the cytoplasm and participates in the cellular 
      transition of reprogramming. Upon adipogenic induction, Ddx6 dynamically 
      accumulated to form PBs with a binding partner, 4E-T, at the early phase prior to 
      emergence of intracellular lipid droplets. In contrast, preadipocytes with Ddx6 
      knockout (KO) or 4E-T knockdown (KD) failed to generate PBs, resulting in 
      significant suppression of adipogenesis. Transcription factors related to 
      preadipocytes and negative regulators of adipogenesis that were not expressed 
      under adipogenic stimulation were maintained in Ddx6-KO and 4E-T-KD preadipocytes 
      under adipogenic induction. Elimination of Dlk1, a major negative regulator of 
      adipogenesis, in 3T3L1 Ddx6-KO cells did not restore adipogenic differentiation 
      capacity to any extent. Similar to murine cells, human primary mesenchymal stem 
      cells, which can differentiate into adipocytes upon stimulation with adipogenic 
      cocktails, required DDX6 to maturate into adipocytes. Therefore, RNA decay of the 
      entire parental transcriptome, rather than removal of a strong negative 
      regulator, could be indispensable for adipogenesis.
FAU - Maeda, Ryotaro
AU  - Maeda R
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Kami, Daisuke
AU  - Kami D
AD  - Department of Regenerative Medicine, Graduate School of Medicine, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Shikuma, Akira
AU  - Shikuma A
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Suzuki, Yosuke
AU  - Suzuki Y
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Taya, Toshihiko
AU  - Taya T
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Matoba, Satoaki
AU  - Matoba S
AUID- ORCID: 0000-0002-9373-4331
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Gojo, Satoshi
AU  - Gojo S
AUID- ORCID: 0000-0001-8115-7816
AD  - Department of Regenerative Medicine, Graduate School of Medicine, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan. gojos@koto.kpu-m.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210317
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.7.-. (Ddx6 protein, mouse)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Adipogenesis/*genetics
MH  - Animals
MH  - DEAD-box RNA Helicases/*metabolism
MH  - Humans
MH  - Mice
MH  - Proto-Oncogene Proteins/*metabolism
MH  - RNA Stability/*genetics
MH  - Transfection
PMC - PMC7969960
COIS- The authors declare no competing interests.
EDAT- 2021/03/19 06:00
MHDA- 2021/10/06 06:00
PMCR- 2021/03/17
CRDT- 2021/03/18 06:16
PHST- 2020/10/07 00:00 [received]
PHST- 2021/02/19 00:00 [accepted]
PHST- 2021/02/16 00:00 [revised]
PHST- 2021/03/18 06:16 [entrez]
PHST- 2021/03/19 06:00 [pubmed]
PHST- 2021/10/06 06:00 [medline]
PHST- 2021/03/17 00:00 [pmc-release]
AID - 10.1038/s41419-021-03537-7 [pii]
AID - 3537 [pii]
AID - 10.1038/s41419-021-03537-7 [doi]
PST - epublish
SO  - Cell Death Dis. 2021 Mar 17;12(4):285. doi: 10.1038/s41419-021-03537-7.