Deadenylation of maternal mRNAs mediated by miR-427 in Xenopus laevis embryos

Abstract

We show that microRNA-427 (miR-427) mediates the rapid deadenylation of maternal mRNAs after the midblastula transition (MBT) of Xenopus laevis embryogenesis. By MBT, the stage when the embryonic cell cycle is remodeled and zygotic transcription of mRNAs is initiated, each embryo has accumulated ;10 9 molecules of miR-427 processed from multimeric primiR-427 transcripts synthesized after fertilization. We demonstrate that the maternal mRNAs for cyclins A1 and B2 each contain a single miR-427 target sequence, spanning less than 30 nucleotides, that is both necessary and sufficient for deadenylation, and that inactivation of miR-427 leads to stabilization of the mRNAs. Although this deadenylation normally takes place after MBT, exogenous miRNAs produced prematurely in vivo can promote deadenylation prior to MBT, indicating that turnover of the maternal mRNAs is limited by the amount of accumulated miR-427. Injected transcripts comprised solely of the cyclin mRNA 39 untranslated regions or bearing a 59 ApppG cap undergo deadenylation, showing that translation of the targeted RNA is not required. miR-427 is not unique in promoting deadenylation, as an unrelated miRNA, let-7, can substitute for miR-427 if the reporter RNA contains an appropriate let-7 target site. We propose that miR-427, like the orthologous miR-430 of zebrafish, functions to down-regulate expression of maternal mRNAs early in development.

Efectos de los RNAm maternos sobre la maduración del ovocito y el desarrollo embrionario temprano en mamíferos

“…In Xenopus, Zebrafish and mouse this mechanism occurs because happens a deadenylation of the extreme 3´UTR of the RNAm promoted by the CCR4/NOT complex, which in turn was activated by its bond with the protein GW182, which in turn interacts with the RISCs via miRNA or endo-siRNA (102,103) . The action of miRNAs on maternal mRNA degradation has been clear in Zebrafish embryos, which shows that the miR430 is abundant in the embryonic activation point, just at the moment the degradation of the maternal transcripts takes place (44) .…”

“…En Zebrafish, Xenopus y ratón este mecanismo se da debido a que sucede una desadenilación del extremo 3´UTR del RNAm promovida por el complejo CCR4/NOT, que a su vez fue activado por su unión con la proteína GW182, que a su vez interacciona con el RISCs vía miRNA o endosiRNA (102,103) . La acción de miRNAs sobre la degradación de RNAm maternos ha quedado clara en embriones del Zebrafish, donde se observa que el miR430 es abundante en el punto de la activación embrionaria, justo en el momento en que sucede la degradación de los transcritos maternos (44) .…”

The microRNAs important for ovarian and early embryonic development in cattle

“…However, these studies focused only on 3' UTRs targeting miRNAs generated by canonical Dicer-and DGCR8-dependent pathways, while other miRNAs targeting the open reading frame (ORF) of mRNAs and/or generated by a noncanonical DGCR8-independent pathway were not investigated. miRNAs such as miRNA-430 in zebrafish, miRNA-427 in Xenopus, and miRNA-21 in rainbow trout have been shown to be present in early embryos prior to embryonic genome activation, and these miRNAs are responsible for degradation of maternal transcripts (42)(43)(44)(45). In bovine early embryos, miR-21 and miR-130a showed significant increases during the 1-8 cell stage (46).…”

T-cell internal antigen 1 counteracts somatic RNA degradation during early Xenopus embryogenesis

“…This transition also involves the degradation of a large fraction of maternal mRNAs (reviewed in Tadros and Lipshitz, 2009;Langley et al, 2014). In zebrafish, Drosophila and Xenopus, this degradation of maternal mRNAs is mediated by microRNAs (miR) (Giraldez et al, 2006;Bushati et al, 2008;Lund et al, 2009).…”