PMID- 24804980
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20220408
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Print)
IS  - 1420-682X (Linking)
VI  - 71
IP  - 22
DP  - 2014 Nov
TI  - miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF.
PG  - 4443-56
LID - 10.1007/s00018-014-1628-x [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a secreted protein of the 
      neurotrophin family that regulates brain development, synaptogenesis, memory and 
      learning, as well as development of peripheral organs, such as angiogenesis in 
      the heart and postnatal growth and repair of skeletal muscle. However, while 
      precise regulation of BDNF levels is an important determinant in defining the 
      biological outcome, the role of microRNAs (miRs) in modulating BDNF expression 
      has not been extensively analyzed. Using in silico approaches, reporter systems, 
      and analysis of endogenous BDNF, we show that miR-1, miR-10b, miR-155, and 
      miR-191 directly repress BDNF through binding to their predicted sites in BDNF 
      3'UTR. We find that the overexpression of miR-1 and miR-10b suppresses endogenous 
      BDNF protein levels and that silencing endogenous miR-10b increases BDNF mRNA and 
      protein levels. Furthermore, we show that miR-1/206 binding sites within BDNF 
      3'UTR are used in differentiated myotubes but not in undifferentiated myoblasts. 
      Finally, our data from two cell lines suggest that endogenous miR-1/206 and 
      miR-10 family miRs act cooperatively in suppressing BDNF through their predicted 
      sites in BDNF 3'UTR. In conclusion, our results highlight miR-1, miR-10b, 
      miR-155, and miR-191 as novel regulators of BDNF long and short 3'UTR isoforms, 
      supporting future research in different physiological and pathological contexts.
FAU - Varendi, Kart
AU  - Varendi K
AD  - Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland.
FAU - Kumar, Anmol
AU  - Kumar A
FAU - Harma, Mari-Anne
AU  - Harma MA
FAU - Andressoo, Jaan-Olle
AU  - Andressoo JO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140508
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MIRN10 microRNA, mouse)
RN  - 0 (MIRN191 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn1 microRNA, mouse)
RN  - 0 (Mirn155 microRNA, mouse)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cell Line
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Sequence Alignment
PMC - PMC4207943
EDAT- 2014/05/09 06:00
MHDA- 2014/12/23 06:00
PMCR- 2014/05/08
CRDT- 2014/05/09 06:00
PHST- 2013/11/05 00:00 [received]
PHST- 2014/04/13 00:00 [accepted]
PHST- 2014/04/01 00:00 [revised]
PHST- 2014/05/09 06:00 [entrez]
PHST- 2014/05/09 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
PHST- 2014/05/08 00:00 [pmc-release]
AID - 1628 [pii]
AID - 10.1007/s00018-014-1628-x [doi]
PST - ppublish
SO  - Cell Mol Life Sci. 2014 Nov;71(22):4443-56. doi: 10.1007/s00018-014-1628-x. Epub 
      2014 May 8.