PMID- 33080252
OWN - NLM
STAT- MEDLINE
DCOM- 20210414
LR  - 20210414
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Linking)
VI  - 469
DP  - 2021 Jan 1
TI  - Fine-tuning of the PAX-SIX-EYA-DACH network by multiple microRNAs controls embryo 
      myogenesis.
PG  - 68-79
LID - S0012-1606(20)30276-1 [pii]
LID - 10.1016/j.ydbio.2020.10.005 [doi]
AB  - MicroRNAs (miRNAs), short non-coding RNAs, which act post-transcriptionally to 
      regulate gene expression, are of widespread significance during development and 
      disease, including muscle disease. Advances in sequencing technology and 
      bioinformatics led to the identification of a large number of miRNAs in 
      vertebrates and other species, however, for many of these miRNAs specific roles 
      have not yet been determined. LNA in situ hybridisation has revealed expression 
      patterns of somite-enriched miRNAs, here we focus on characterising the functions 
      of miR-128. We show that antagomiR-mediated knockdown (KD) of miR-128 in 
      developing chick somites has a negative impact on skeletal myogenesis. 
      Computational analysis identified the transcription factor EYA4 as a candidate 
      target consistent with the observation that miR-128 and EYA4 display similar 
      expression profiles. Luciferase assays confirmed that miR-128 interacts with the 
      EYA4 3'UTR. In vivo experiments also suggest that EYA4 is regulated by miR-128. 
      EYA4 is a member of the PAX-SIX-EYA-DACH (PSED) network of transcription factors. 
      Therefore, we identified additional candidate miRNA binding sites in the 3'UTR of 
      SIX1/4, EYA1/2/3 and DACH1. Using the miRanda algorithm, we found sites for 
      miR-128, as well as for other myogenic miRNAs, miR-1a, miR-206 and miR-133a, some 
      of these were experimentally confirmed as functional miRNA target sites. Our 
      results reveal that miR-128 is involved in regulating skeletal myogenesis by 
      directly targeting EYA4 with indirect effects on other PSED members, including 
      SIX4 and PAX3. Hence, the inhibitory effect on myogenesis observed after miR-128 
      knockdown was rescued by concomitant knockdown of PAX3. Moreover, we show that 
      the PSED network of transcription factors is co-regulated by multiple 
      muscle-enriched microRNAs.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Viaut, Camille
AU  - Viaut C
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
FAU - Weldon, Shannon
AU  - Weldon S
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
FAU - Munsterberg, Andrea
AU  - Munsterberg A
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. Electronic address: 
      A.Munsterberg@uea.ac.uk.
LA  - eng
GR  - BB/K003437/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/N007034/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201017
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (PAX3 Transcription Factor)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Animals
MH  - Chick Embryo
MH  - *Gene Expression Regulation, Developmental
MH  - Homeodomain Proteins/genetics/metabolism
MH  - MicroRNAs/*metabolism
MH  - Muscle Development/*genetics
MH  - Muscle, Skeletal/*embryology/metabolism
MH  - PAX3 Transcription Factor/genetics/metabolism
MH  - Somites/embryology/metabolism
MH  - Transcription Factors/*genetics/metabolism
OTO - NOTNLM
OT  - Chicken embryo
OT  - EYA4
OT  - PSED network
OT  - Somite myogenesis
OT  - miR-128
OT  - myomiRs
EDAT- 2020/10/21 06:00
MHDA- 2021/04/15 06:00
CRDT- 2020/10/20 20:07
PHST- 2020/02/20 00:00 [received]
PHST- 2020/10/06 00:00 [revised]
PHST- 2020/10/14 00:00 [accepted]
PHST- 2020/10/21 06:00 [pubmed]
PHST- 2021/04/15 06:00 [medline]
PHST- 2020/10/20 20:07 [entrez]
AID - S0012-1606(20)30276-1 [pii]
AID - 10.1016/j.ydbio.2020.10.005 [doi]
PST - ppublish
SO  - Dev Biol. 2021 Jan 1;469:68-79. doi: 10.1016/j.ydbio.2020.10.005. Epub 2020 Oct 
      17.