PMID- 25047835
OWN - NLM
STAT- MEDLINE
DCOM- 20141111
LR  - 20211203
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 34
IP  - 19
DP  - 2014 Oct 1
TI  - Role of the mTORC1 complex in satellite cell activation by RNA-induced 
      mitochondrial restoration: dual control of cyclin D1 through microRNAs.
PG  - 3594-606
LID - 10.1128/MCB.00742-14 [doi]
AB  - During myogenesis, satellite stem cells (SCs) are induced to proliferate and 
      differentiate to myogenic precursors. The role of energy sensors such as the 
      AMP-activated protein kinase (AMPK) and the mammalian Target of Rapamycin (mTOR) 
      in SC activation is unclear. We previously observed that upregulation of ATP 
      through RNA-mediated mitochondrial restoration (MR) accelerates SC activation 
      following skeletal muscle injury. We show here that during regeneration, the 
      AMPK-CRTC2-CREB and Raptor-mTORC-4EBP1 pathways were rapidly activated. The 
      phosho-CRTC2-CREB complex was essential for myogenesis and activated 
      transcription of the critical cell cycle regulator cyclin D1 (Ccnd1). Knockdown 
      (KD) of either mTORC or its subunit Raptor delayed SC activation without 
      influencing the differentiation program. KD of 4EBP1 had no effect on SC 
      activation but enhanced myofiber size. mTORC1 positively regulated Ccnd1 
      translation but destabilized Ccnd1 mRNA. These antithetical effects of mTORC1 
      were mediated by two microRNAs (miRs) targeted to the 3' untranslated region 
      (UTR) of Ccnd1 mRNA: miR-1 was downregulated in mTORC-KD muscle, and depletion of 
      miR-1 resulted in increased levels of mRNA without any effect on Ccnd1 protein. 
      In contrast, miR-26a was upregulated upon mTORC depletion, while anti-miR-26a 
      oligonucleotide specifically stimulated Ccnd1 protein expression. Thus, mTORC may 
      act as a timer of satellite cell proliferation during myogenesis.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Jash, Sukanta
AU  - Jash S
AD  - Genetic Engineering Laboratory, CSIR-Indian Institute of Chemical Biology, 
      Calcutta, India.
FAU - Dhar, Gunjan
AU  - Dhar G
AD  - Genetic Engineering Laboratory, CSIR-Indian Institute of Chemical Biology, 
      Calcutta, India.
FAU - Ghosh, Utpalendu
AU  - Ghosh U
AD  - Genetic Engineering Laboratory, CSIR-Indian Institute of Chemical Biology, 
      Calcutta, India.
FAU - Adhya, Samit
AU  - Adhya S
AD  - Genetic Engineering Laboratory, CSIR-Indian Institute of Chemical Biology, 
      Calcutta, India nilugrandson@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140721
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (CRTC2 protein, rat)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (MIRN1 microRNA, rat)
RN  - 0 (MIRN26 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Mitochondrial)
RN  - 0 (Trans-Activators)
RN  - 136601-57-5 (Cyclin D1)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Cell Proliferation
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclin D1/*genetics/*metabolism
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Muscle Development
MH  - Muscle, Skeletal/*injuries
MH  - RNA/metabolism
MH  - RNA Stability
MH  - RNA, Mitochondrial
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Satellite Cells, Skeletal Muscle/*physiology
MH  - Stem Cells/*physiology
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Trans-Activators/metabolism
PMC - PMC4187730
EDAT- 2014/07/23 06:00
MHDA- 2014/11/12 06:00
PMCR- 2015/04/01
CRDT- 2014/07/23 06:00
PHST- 2014/07/23 06:00 [entrez]
PHST- 2014/07/23 06:00 [pubmed]
PHST- 2014/11/12 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - MCB.00742-14 [pii]
AID - 00742-14 [pii]
AID - 10.1128/MCB.00742-14 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2014 Oct 1;34(19):3594-606. doi: 10.1128/MCB.00742-14. Epub 2014 
      Jul 21.