title: Reciprocal regulation of miRNAs and piRNAs in embryonic development.
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.
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: W W
authors.initials: WW
authors.lastname: Du
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Xuan
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Chemistry and Centre for Research on Biomolecular Interactions, York University, 4700 Keele Street, Toronto, ON M3J 1P3, Canada.
authors.forename: S N
authors.initials: SN
authors.lastname: Krylov
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: B B
authors.initials: BB
authors.lastname: Yang
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D004251:DNA Transposable Elements / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D005298:Fertility; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015053:Zygote / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D004251:DNA Transposable Elements; C000715535:Dnmt3a protein, mouse; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; C448521:Piwil2 protein, mouse; D034741:RNA, Small Interfering; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A