Abstract
MicroRNAs (miRNAs) and piwi-interacting RNAs (piRNAs) are two classes of small noncoding RNAs, both of which play roles in regulating tissue development. It is unknown whether these distinct classes of noncoding RNAs can regulate one another. Here we show that ectopic expression of miR-17 inhibited mouse fertility and early embryonic development. Specifically, we found that the piRNA amplification loop was repressed by miR-17-5p, leading to increased levels of transposition mutagenesis. This occurred by suppressing the amplification loop of piRNAs with an identical 5′ sequence and by targeting Mili/Miwi2, an essential component of the piRNA amplification loop, and the DNA methyltransferase, Dnmt3a. We also found that increased levels of piRNAs could compete with miRNAs for target binding, resulting in increased expression of Dnmt3a and Mili. Increased Dnmt3a levels could in turn block miR-17-5p expression, while increased Mili expression could accelerate piRNA amplification and inhibit transposon generation, favoring embryonic development. We report for the first time the reciprocal regulation between miRNAs and piRNAs in mouse embryonic development.
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Abbreviations
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- FBS:
-
fetal bovine serum
- GFP:
-
green fluorescent protein
- siRNA:
-
small interfering RNA
- miRNA:
-
microRNA
- 3′-UTR:
-
3′-untranslated region
- Dnmt3a:
-
DNA (cytosine-5)-methyltransferase 3A
- Piwi:
-
P-element induced wimpy testis
- MIWI2:
-
mouse piwi 2
- MILI:
-
miwi-like
- piRNA:
-
piwi-interacting RNA
- Line-1:
-
long interspersed elements
- MuERV:
-
murine endogenous retrovirus
- IAP:
-
intracisternal A-particle
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Acknowledgements
The authors thank Drs. Chengyan He and Ling Fang (China-Japan Union Hospital of Jilin University) and Dr. Xiangling Yang (The Sixth Affiliated Hospital, Sun Yat-sen University) for technical assistance. This work was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC; 227937-2012) to BBY and a grant from the Canadian Institutes of Health Research (CHRP 462341-2014) and Natural Sciences and Engineering Research Council of Canada (CPG 134747) to SNK and BBY. BBY is the recipient of a Career Investigator Award (CI 7418) from the Heart and Stroke Foundation of Ontario. WWD is supported by a fellowship from the Canadian Breast Cancer Foundation of Ontario.
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Du, W., Yang, W., Xuan, J. et al. Reciprocal regulation of miRNAs and piRNAs in embryonic development. Cell Death Differ 23, 1458–1470 (2016). https://doi.org/10.1038/cdd.2016.27
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DOI: https://doi.org/10.1038/cdd.2016.27
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