PMID- 27097372
OWN - NLM
STAT- MEDLINE
DCOM- 20170106
LR  - 20211203
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 15
IP  - 8
DP  - 2016
TI  - microRNA-496 - A new, potentially aging-relevant regulator of mTOR.
PG  - 1108-16
LID - 10.1080/15384101.2016.1158360 [doi]
AB  - Recent findings strongly support a role for small regulatory RNAs in the 
      regulation of human lifespan yet little information exists about the precise 
      underlying mechanisms. Although extensive studies on model organisms have 
      indicated that reduced activity of the nutrient response pathway, for example as 
      a result of dietary restriction, can extend lifespan through the suppression of 
      the protein kinase mechanistic target of rapamycin (mTOR), it still is subject of 
      debate whether this mechanism is operative in humans as well. Here, we present 
      findings indicating that human microRNA (miR)-496 targets 2 sites within the 
      human mTOR 3'UTR. Coexpression of miR-496 with different fusion transcripts, 
      consisting of the luciferase transcript and either wild-type mTOR 3'UTR or mTOR 
      3'UTR transcript with the miR-496 binding sites singly or combined mutated, 
      confirmed this prediction and revealed cooperativity between the 2 binding sites. 
      miR-496 reduced the mTOR protein level in HeLa-K cells, and the levels of miR-496 
      and mTOR protein were inversely correlated in Peripheral Blood Mononuclear Cells 
      (PBMC), with old individuals (n = 40) harbouring high levels of miR-496 relative 
      to young individuals (n = 40). Together, these findings point to the possibility 
      that miR-496 is involved in the regulation of human aging through the control of 
      mTOR.
FAU - Rubie, Claudia
AU  - Rubie C
AD  - a Department of General-, Visceral-, Vascular- and Pediatric Surgery , University 
      of Saarland Medical Center , Homburg/Saar , Germany.
FAU - Kolsch, Kathrin
AU  - Kolsch K
AD  - a Department of General-, Visceral-, Vascular- and Pediatric Surgery , University 
      of Saarland Medical Center , Homburg/Saar , Germany.
FAU - Halajda, Beata
AU  - Halajda B
AD  - a Department of General-, Visceral-, Vascular- and Pediatric Surgery , University 
      of Saarland Medical Center , Homburg/Saar , Germany.
FAU - Eichler, Hermann
AU  - Eichler H
AD  - b Institute of Clinical Haemostaseology and Transfusion Medicine, University of 
      Saarland Medical Center , Homburg/Saar , Germany.
FAU - Wagenpfeil, Stefan
AU  - Wagenpfeil S
AD  - c Institute of Medical Biometrics, Epidemiology, and Medical Informatics (IMBEI), 
      University of Saarland Medical Center , Homburg/Saar , Germany.
FAU - Roemer, Klaus
AU  - Roemer K
AD  - d Jose Carreras Research Center, University of Saarland Medical Center , 
      Homburg/Saar , Germany.
FAU - Glanemann, Matthias
AU  - Glanemann M
AD  - a Department of General-, Visceral-, Vascular- and Pediatric Surgery , University 
      of Saarland Medical Center , Homburg/Saar , Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MIRN496 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (RNA, Messenger)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*genetics
MH  - Base Sequence
MH  - Blood Donors
MH  - Down-Regulation/genetics
MH  - Female
MH  - HeLa Cells
MH  - Healthy Volunteers
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism
MH  - Luciferases/metabolism
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - MicroRNAs/genetics/*metabolism
MH  - Middle Aged
MH  - Multiprotein Complexes/metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - RNA, Messenger/genetics/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Young Adult
PMC - PMC4889276
OTO - NOTNLM
OT  - Human aging
OT  - PBMC
OT  - gene regulation
OT  - mTOR
OT  - microRNA
EDAT- 2016/04/21 06:00
MHDA- 2017/01/07 06:00
PMCR- 2017/04/20
CRDT- 2016/04/21 06:00
PHST- 2016/04/21 06:00 [entrez]
PHST- 2016/04/21 06:00 [pubmed]
PHST- 2017/01/07 06:00 [medline]
PHST- 2017/04/20 00:00 [pmc-release]
AID - 1158360 [pii]
AID - 10.1080/15384101.2016.1158360 [doi]
PST - ppublish
SO  - Cell Cycle. 2016;15(8):1108-16. doi: 10.1080/15384101.2016.1158360.