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Status |
Public on Apr 06, 2018 |
Title |
An Evolutionarily-Conserved Long Noncoding RNA Myolinc Regulates muscle differentiation [array_knockdown] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of lncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identified a novel muscle-enriched lncRNA called "Myolinc (AK142388)", which we functionally characterized in the C2C12 myoblast cell line. Myolinc is predominately localized in the nucleus, and its levels increase upon induction of the differentiation. Knockdown of Myolinc impairs the expression of myogenic regulatory factors and formation of multinucleated myotubes in cultured myoblasts. Myolinc also regulates the expression of Filip1 in a cis-manner. Similar to Myolinc, knockdown of Filip1 inhibits myogenic differentiation. Furthermore, Myolinc binds to TAR DNA-binding protein 43 (TDP-43), a DNA/RNA-binding protein that regulates the expression of muscle genes (e.g. Acta1 and MyoD). Knockdown of TDP-43 inhibits myogenic differentiation. We also show that Myolinc-TDP-43 interaction is essential for the binding of TDP-43 to the promoter regions of muscle marker genes. Finally, we show that silencing of Myolinc inhibits skeletal muscle regeneration in adult mice. Altogether, our study identifies a novel lncRNA that controls key regulatory networks of myogenesis.
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Overall design |
Using C2C12 cells, we performed microarray experiments (n=2) for each time point and condition. “Day_2” dataset: siMyolinc-knockdown C2C12 cells on day 2 of the differentation were compared to C2C12 cells transfected with siRNA against scramble control (siScr) and differentiated for 2 days. “Undiff-Day_2” dataset: siMyolinc-knockdown C2C12 cells on day 2 of the differentation were compared to normally cultured C2C12 cells in the growth medium (“Undiff”), one and two days after the differentiation (“Day_1” and “Day_2”, respectively).
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Web link |
https://academic.oup.com/jmcb/advance-article/doi/10.1093/jmcb/mjy025/4959340
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Contributor(s) |
Uchida S, Militello G |
Citation(s) |
29618024 |
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Submission date |
Jun 02, 2015 |
Last update date |
Mar 04, 2019 |
Contact name |
Shizuka Uchida |
E-mail(s) |
heart.lncrna@gmail.com, suc@dcm.aau.dk
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Organization name |
Aalborg University
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Department |
Department of Clinical Medicine
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Lab |
Center for RNA Medicine
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Street address |
Frederikskaj 10B, 2. (building C)
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City |
Copenhagen SV |
ZIP/Postal code |
DK-2450 |
Country |
Denmark |
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Platforms (1) |
GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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Samples (20)
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GSM1702830 |
siScramble-transfected at Day 2 of differentiation, biological rep1 [Day2 dataset] |
GSM1702831 |
siScramble-transfected at Day 2 of differentiation, biological rep2 [Day2 dataset] |
GSM1702832 |
siMyolinc.1-transfected at Day 2 of differentiation, biological rep1 [Day2 dataset] |
GSM1702833 |
siMyolinc.1-transfected at Day 2 of differentiation, biological rep2 [Day2 dataset] |
GSM1702834 |
siMyolinc.2-transfected at Day 2 of differentiation, biological rep1 [Day2 dataset] |
GSM1702835 |
siMyolinc.2-transfected at Day 2 of differentiation, biological rep2 [Day2 dataset] |
GSM1702836 |
siMyolinc.3-transfected at Day 2 of differentiation, biological rep1 [Day2 dataset] |
GSM1702837 |
siMyolinc.3-transfected at Day 2 of differentiation, biological rep2 [Day2 dataset] |
GSM1702838 |
Undifferentiated, biological rep1 [Undiff-Day_2 dataset] |
GSM1702839 |
Undifferentiated, biological rep2 [Undiff-Day_2 dataset] |
GSM1702840 |
Day 1 of differentiation, biological rep1 [Undiff-Day_2 dataset] |
GSM1702841 |
Day 1 of differentiation, biological rep2 [Undiff-Day_2 dataset] |
GSM1702842 |
Day 2 of differentiation, biological rep1 [Undiff-Day_2 dataset] |
GSM1702843 |
Day 2 of differentiation, biological rep2 [Undiff-Day_2 dataset] |
GSM1702844 |
siMyolinc.1-transfected at Day 2 of differentiation, biological rep1 [Undiff-Day_2 dataset] |
GSM1702845 |
siMyolinc.1-transfected at Day 2 of differentiation, biological rep2 [Undiff-Day_2 dataset] |
GSM1702846 |
siMyolinc.2-transfected at Day 2 of differentiation, biological rep1 [Undiff-Day_2 dataset] |
GSM1702847 |
siMyolinc.2-transfected at Day 2 of differentiation, biological rep2 [Undiff-Day_2 dataset] |
GSM1702848 |
siMyolinc.3-transfected at Day 2 of differentiation, biological rep1 [Undiff-Day_2 dataset] |
GSM1702849 |
siMyolinc.3-transfected at Day 2 of differentiation, biological rep2 [Undiff-Day_2 dataset] |
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This SubSeries is part of SuperSeries: |
GSE69530 |
A novel long non-coding RNA Myolinc regulates myogenesis through TDP-43 and Filip1 |
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Relations |
BioProject |
PRJNA285792 |
Supplementary file |
Size |
Download |
File type/resource |
GSE69451_RAW.tar |
89.6 Mb |
(http)(custom) |
TAR (of CEL) |
GSE69451_siMyolinc-C2C12-Militello2015.xlsx |
9.7 Mb |
(ftp)(http) |
XLSX |
Processed data included within Sample table |
Processed data are available on Series record |
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