Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis

Ablation of a single miRNA gene rarely leads to a discernable developmental phenotype in mice, in some cases because of compensatory effects by other functionally related miRNAs. Here, we report that simultaneous inactivation of two functionally related miRNA clusters (miR-34b/c and miR-449) encodin...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2014-07, Vol.111 (28), p.E2851-E2857
Main Authors: Wu, Jingwen, Bao, Jianqiang, Kim, Minkyung, Yuan, Shuiqiao, Tang, Chong, Zheng, Huili, Mastick, Grant S, Xu, Chen, Yan, Wei
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Brain
Brain - embryology
Cells
Cilia - genetics
Cilia - metabolism
Gene Expression Regulation, Developmental - physiology
Genetics
Infertility, Male - genetics
Infertility, Male - metabolism
Male
Mice
Mice, Knockout
MicroRNAs - genetics
MicroRNAs - metabolism
Multigene Family - physiology
PNAS Plus
Ribonucleic acid
RNA
Spermatogenesis - physiology
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Summary:Ablation of a single miRNA gene rarely leads to a discernable developmental phenotype in mice, in some cases because of compensatory effects by other functionally related miRNAs. Here, we report that simultaneous inactivation of two functionally related miRNA clusters (miR-34b/c and miR-449) encoding five miRNAs (miR-34b, miR-34c, miR-449a, miR-449b, and miR-449c) led to sexually dimorphic, partial perinatal lethality, growth retardation, and infertility. These developmental defects correlated with the dysregulation of ∼240 target genes, which are mainly involved in three major cellular functions, including cell-fate control, brain development and microtubule dynamics. Our data demonstrate an essential role of a miRNA family in brain development, motile ciliogenesis, and spermatogenesis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1407777111