RNA‐Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation

Abstract

A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA‐binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf 2bp2 (also commonly known as Imp2 ) in mouse embryos causes early embryonic developmental arrest in vitro at the 2‐cell‐stage. Transcriptomics and proteomics analyses of 2‐cell‐stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14 , both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild‐type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 × 10 −9 m IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2‐treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development‐related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.

Roles of N6-Methyladenosine (m6A) in Stem Cell Fate Decisions and Early Embryonic Development in Mammals

“…In addition, miR-670-3p was found to regulate IGF2BP1 and affect apoptosis in PA embryos ( Hao et al, 2020 ). Subsequently, Liu H.B. et al (2019) reported that IGF2BP2 (also known as IMP2) is highly expressed in oocytes and early-stage embryos.…”

“…et al (2019) reported that IGF2BP2 (also known as IMP2) is highly expressed in oocytes and early-stage embryos. IGF2BP2 deletion was not essential for oocyte maturation, while IGF2BP2-knockout mice exhibited female infertility ( Liu H.B. et al, 2019 ).…”

“…et al, 2019 ). Moreover, maternal deletion of IGF2BP2 caused embryos to arrest at the 2-cell stage ( Liu H.B. et al, 2019 ).…”

“…et al, 2019 ). Transcriptome and proteome analyses suggested that knockout of IGF2BP2 inhibited the transcription and translation of downstream genes related to ZGA, such as CCAR1 and RPS14 ( Liu H.B. et al, 2019 ).…”

YTHDF2 Regulates Maternal Transcriptome Degradation and Embryo Development in Goat

“…Recognition of m 6 A mRNA by YTHDF2 within the GACU/A consensus is associated with mRNA destabilization and degradation (Du et al, 2016), suggesting that maternal mRNA clearance is also under the tight control of m 6 A. Indeed, an increasing number of studies demonstrated that knockout of IGF2BP2 (Liu et al, 2019), YTHDC2 (Hsu et al, 2017), and YTHDF2 (Zhao et al, 2017) impaired maternal mRNA elimination. Moreover, zygotic transcription is first detected at the late 1-cell stage, whereas the majority of maternal mRNAs are removed by the 2-cell stage in mice (Sha et al, 2019a;Vastenhouw et al, 2019), suggesting that there is a complex crosstalk of maternal and zygotic products in regulating MZT, thus ensuring timely transfer of developmental control (Sha et al, 2019b).…”