PMID- 32608991
OWN - NLM
STAT- MEDLINE
DCOM- 20201022
LR  - 20211204
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 319
IP  - 2
DP  - 2020 Aug 1
TI  - MicroRNA-99b-5p downregulates protein synthesis in human primary myotubes.
PG  - C432-C440
LID - 10.1152/ajpcell.00172.2020 [doi]
AB  - microRNAs (miRNAs) are important regulators of cellular homeostasis and exert 
      their effect by directly controlling protein expression. We have previously 
      reported an age-dependent negative association between microRNA-99b (miR-99b-5p) 
      expression and muscle protein synthesis in human muscle in vivo. Here we 
      investigated the role of miR-99b-5p as a potential negative regulator of protein 
      synthesis via inhibition of mammalian target for rapamycin (MTOR) signaling in 
      human primary myocytes. Overexpressing miR-99b-5p in human primary myotubes from 
      young and old subjects significantly decreased protein synthesis with no effect 
      of donor age. A binding interaction between miR-99b-5p and its putative binding 
      site within the MTOR 3'-untranslated region (UTR) was confirmed in C(2)C(12) 
      myoblasts. The observed decline in protein synthesis was, however, not associated 
      with a suppression of the MTOR protein but of its regulatory associated protein 
      of mTOR complex 1 (RPTOR). These results demonstrate that modulating the 
      expression levels of a miRNA can regulate protein synthesis in human muscle cells 
      and provide a potential mechanism for muscle wasting in vivo.
FAU - Zacharewicz, Evelyn
AU  - Zacharewicz E
AD  - Institute for Physical Activity and Nutrition, School of Exercise and Nutrition 
      Sciences, Deakin University, Geelong, Victoria, Australia.
FAU - Kalanon, Ming
AU  - Kalanon M
AD  - Institute for Physical Activity and Nutrition, School of Exercise and Nutrition 
      Sciences, Deakin University, Geelong, Victoria, Australia.
FAU - Murphy, Robyn M
AU  - Murphy RM
AUID- ORCID: 0000-0003-3697-589X
AD  - Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La 
      Trobe University, Melbourne, Victoria, Australia.
FAU - Russell, Aaron P
AU  - Russell AP
AUID- ORCID: 0000-0002-7323-9501
AD  - Institute for Physical Activity and Nutrition, School of Exercise and Nutrition 
      Sciences, Deakin University, Geelong, Victoria, Australia.
FAU - Lamon, Severine
AU  - Lamon S
AUID- ORCID: 0000-0002-3271-6551
AD  - Institute for Physical Activity and Nutrition, School of Exercise and Nutrition 
      Sciences, Deakin University, Geelong, Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200701
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MIRN99 microRNA, human)
RN  - 0 (MicroRNAs)
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 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Animals
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1/genetics
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Muscle Fibers, Skeletal/*metabolism
MH  - Myoblasts/metabolism
MH  - Protein Biosynthesis/*genetics
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases/*genetics
OTO - NOTNLM
OT  - microRNA
OT  - muscle
OT  - primary muscle cells
OT  - protein synthesis
EDAT- 2020/07/02 06:00
MHDA- 2020/10/23 06:00
CRDT- 2020/07/02 06:00
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2020/10/23 06:00 [medline]
PHST- 2020/07/02 06:00 [entrez]
AID - 10.1152/ajpcell.00172.2020 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2020 Aug 1;319(2):C432-C440. doi: 
      10.1152/ajpcell.00172.2020. Epub 2020 Jul 1.