microRNAs, the cell's Nepenthe: clearing the past during the maternal-to-zygotic transition and cellular reprogramming

Abstract

The maternal-to-zygotic transition (MZT) is a universal step in animal development characterized by two major events: activation of zygotic transcription and degradation of maternally provided mRNAs. How zygotic gene products instruct the degradation of maternal messages remains a long-standing question in biology. MicroRNAs (miRNAs) have recently emerged as widespread regulators of gene expression. miRNAs control temporal and spatial gene expression by both accelerating the decay of mRNAs from previous developmental stages and modulating the levels of actively transcribed genes. In this review, I discuss recent studies of the roles of miRNAs during the maternal-to-zygotic transition and cellular reprogramming, where they reshape transcriptional landscapes to facilitate the establishment of novel cellular states.

Figure 1. MicroRNAs clear the cell’s transcriptional landscape during developmental transitions

(A) Diagram of a cell in two different states. The expression of a miRNA (hairpin) in the second state leads to the clearance of some transcripts (red) and the partial downregulation of other targets (green). (B,C) Schematic representation of levels for different mRNAs and a miRNA in the maternal-to-zygotic transition in the presence (B) and the absence (C) of a miRNA. The different curves represent the degradation profiles of maternal (red, blue) and maternal-zygotic (green) transcripts that are regulated by the miRNA during the maternal-to-zygotic transition or during reprogramming., resulting in a rapid decay of the mRNA levels. Targeting of the green transcript by the miRNA allows the cell to regulate the steady state levels of this mRNA. (D) Diagram representing known examples of miRNAs that regulate the clearance of maternal transcripts during the maternal-to-zygotic transition in different organisms. (E) Reprogramming of somatic cells to a pluripotent state. Introducing the mouse ortholog of miR-430 (miR-294) into differentiated cells together with Oct4 Sox2, and Klf4 enhances the reprogramming efficiency.

Figure 2. RNA binding proteins modulate miRNA-mediated repression of maternal mRNAs in germ cells

Model for the post-transcriptional regulation of mRNA targets by miRNAs. (A) Target mRNA translation: interaction between poly(A) binding protein (PABP) on poly(A) tail with translation initiation factors eIF4G/eIF4E on Cap stimulates translation. (B) miRNA-mediated target mRNA deadenylation: The miRNA induced silencing complex (miRISC) is recruited to the 3’ UTR of target mRNA and accelerates deadenylation. (C) Binding of the DAZL to the 3’UTR of the target (Tdrd7) antagonizes miRNA-mediated repression by promoting polyadenylation. (D) Binding of Dead end (Dnd) to the 3’UTR of nanos1 blocks the binding of the miRISC to the target, and antagonizes miRNA-mediated repression of nanos1 in germ cells.