Maternal microRNAs are essential for mouse zygotic development

Abstract

MicroRNAs (miRNAs) have important roles in diverse cellular processes, but little is known about their identity and functions during early mammalian development. Here, we show the effects of the loss of maternal inheritance of miRNAs following specific deletion of Dicer from growing oocytes. The mutant mature oocytes were almost entirely depleted of all miRNAs, and they failed to progress through the first cell division, probably because of disorganized spindle formation. By comparing single-cell cDNA microarray profiles of control and mutant oocytes, our data are compatible with the notion that a large proportion of the maternal genes are directly or indirectly under the control of miRNAs, which demonstrates that the maternal miRNAs are essential for the earliest stages of mouse embryonic development.Supplemental material is available at http://www.genesdev.org.Received November 20, 2006; revised version accepted January 29, 2007. MicroRNAs (miRNAs) are a large family of short noncoding RNAs (17-25 nucleotides) (He and Hannon 2004). A key function of miRNAs is to repress expression of their target genes through sequence complementation, which reduces the abundance of the target mRNAs and/ or inhibits their translation (Bartel 2004;Bagga et al. 2005). MiRNA genes are first transcribed into miRNA primary transcripts by RNA polymerase II (Kim 2005). These primary transcripts are then processed into miRNA precursors by the Drosha/DGCR8 complex and transported from the nucleus to the cytoplasm. Finally, Dicer processes the miRNA precursors into mature miRNAs. From previous studies, Dicer seems to be critical for early mouse development since its loss of function is embryonic lethal at embryonic day 7.5 (E7.5) (Bernstein et al. 2003).In this study, we have examined the role of miRNAs in the mouse oocyte. The mature oocyte contains a number of molecules that are manufactured during oocyte maturation and utilized during early stages of development before activation of the embryonic genome (Dean 2002). It is likely that miRNAs would also be present in the oocyte, but no information is yet available in the mouse. The purpose of this study was to determine if there is significant inheritance of maternal miRNAs in mammalian zygotes, and to investigate if they play a critical role in early mammalian development. We have investigated how the loss of Dicer affects synthesis of miRNA during oocyte maturation and their impact on mRNA and early development. Results and DiscussionFirst, we decided to investigate if there is significant biogenesis of miRNAs in developing oocytes, and their inheritance in the zygote. We therefore examined expression of miRNAs in single cells during oogenesis by a real-time PCR-based miRNA expression profiling method that we recently developed (C. Tang et al. 2006a,b). We compared the miRNA expression profiles of growing oocytes obtained from females 15-16 d after birth (postnatal days 15-16 [P15-P16]) and at P20-P21, and of mature oocytes from adult females. This analysis reveled dynamic chan...

Differentially expressed micoRNAs in human oocytes

“…It was reported that miRNAs directly or indirectly control more than one third of the maternal genes expressed in oocytes [8]. High expressions of Dicer and miRNAs insured normal oocyte maturation and maintained meiotic spindle integrity which is necessary for normal meiotic maturation [10].…”

“…Previously, dynamic changes in miRNA expression during oogenesis have been found in growing mouse oocytes obtained from females 15-16 d after birth (postnatal days 15-16 [P15-P16]), at P20-P21, and mature oocytes from adult females [8]. Several miRNAs, such as miR-103, let-7 d, miR-16, miR-30b and miR-30c, were suggested to play fundamental roles in the meiosis of mouse GVoocytes [9].…”

“…It has been estimated that 30% or more of human mRNAs are regulated by miRNAs [7]. Likewise, miRNAs may also play an important role in modulating gene expression in oocytes [8].…”

“…Dynamic changes in miRNA expression during oogenesis were first revealed by a real-time PCR-based miRNA expression profiling method in single mouse oocytes [8]. A Yan-Wen Xu and Bin Wang contributed equally to this study.…”

“…It has been estimated that 30% or more of human mRNAs are regulated by miRNAs [7]. Likewise, miRNAs may also play an important role in modulating gene expression in oocytes [8].Dynamic changes in miRNA expression during oogenesis were first revealed by a real-time PCR-based miRNA expression profiling method in single mouse oocytes [8]. A Yan-Wen Xu and Bin Wang contributed equally to this study.…”