Nuclear Poly(A)-binding Protein 1-like (PABPN1L) Mediates Cytoplasmic mRNA Decay As a Placeholder during Maternal-to-zygotic Transition
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA578271 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10307311_1.fastq.gz | Fastqsanger.gz | |||
| SRR10307311_2.fastq.gz | Fastqsanger.gz | |||
| SRR10307312_1.fastq.gz | Fastqsanger.gz | |||
| SRR10307312_2.fastq.gz | Fastqsanger.gz | |||
| SRR10307313_1.fastq.gz | Fastqsanger.gz |
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Project description:Maternal mRNA degradation is a critical event of maternal-to-zygotic transition (MZT) that determines the developmental potential of early embryos. Nuclear Poly(A)-binding proteins (PABPNs) are extensively involved in mRNA post-transcriptional regulations, but their functions in mammalian MZT has not been investigated. In this study, we identified a novel maternal-effect factor PABPN1-like (PABPN1L), rather than its ubiquitously expressed homolog PABPN1, as an RNA-binding adapter of the mammalian MZT licensing factor BTG4 which mediates maternal mRNAs clearance. Female Pabpn1l null mice produced morphologically normal oocytes but were infertile owing to early developmental arrest of the resultant embryos at the 1-to-2-cell stages without undergoing ZGA. Deletion of Pabpn1l impairs the deadenylation and degradation of a subset of BTG4-targeted maternal mRNAs during MZT. In addition to recruiting BTG4 to the mRNA 3ʹ-poly(A) tails, PABPN1L is also required for BTG4 protein accumulation in maturing oocytes by protecting BTG4 from SCF-βTrCP1 E3 ubiquitin ligase-mediated polyubiquitination and degradation. This study highlights a noncanonical cytoplasmic function of nuclear poly(A)-binding proteins mRNA turnover as well as its physiological importance during MZT.
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Project description:An embryo starts its life with maternal mRNA clearance, which is crucial for embryonic development. The elimination of maternal transcripts occurs by the joint action of two pathways: the first is a maternally encoded mRNA decay pathway (M-decay), while the second is zygotic genome activation (ZGA)-dependent pathway (Z-decay). However, the zygotic factors triggering maternal mRNA decay in early mammalian embryos remain largely unknown. In this study, we identify the zygotically encoded nuclear poly(A) binding protein 1 (PABPN1) as a factor required for maternal mRNA turnover, with an unpredictable cytoplasmic function. Cytoplasmic PABPN1 docks on 3ʹ-uridylated transcripts, downstream of terminal uridylyl transferases TUT4 and TUT7, and recruits 3ʹ-5ʹ exoribonuclease DIS3L2 to its targets, facilitating the decay of maternal mRNA. Pabpn1-knockout in mice resulted in preimplantation-stage mortality, due to early developmental arrest at the morula stage. This study characterizes the presence of a zygotic destabilizer of maternal mRNA and helps in elucidating the Z-decay process mechanisms, which potentially contribute to human fertility.
2021-11-25 | GSE174032 | GEO
Project description:Maternal mRNA degradation is a critical event of the maternal-to-zygotic transition (MZT) that determines the developmental potential of early embryos. Nuclear Poly(A)-binding proteins (PABPNs) are extensively involved in mRNA post-transcriptional regulation, but their function in the MZT has not been investigated. In this study, we find that the maternally expressed PABPN1-like (PABPN1L), rather than its ubiquitously expressed homolog PABPN1, acts as an mRNA-binding adapter of the mammalian MZT licensing factor BTG4, which mediates maternal mRNA clearance. Female Pabpn1l null mice produce morphologically normal oocytes but are infertile owing to early developmental arrest of the resultant embryos at the 1- to 2-cell stage. Deletion of Pabpn1l impairs the deadenylation and degradation of a subset of BTG4-targeted maternal mRNAs during the MZT. In addition to recruiting BTG4 to the mRNA 3'-poly(A) tails, PABPN1L is also required for BTG4 protein accumulation in maturing oocytes by protecting BTG4 from SCF-βTrCP1 E3 ubiquitin ligase-mediated polyubiquitination and degradation. This study highlights a noncanonical cytoplasmic function of nuclear poly(A)-binding protein in mRNA turnover, as well as its physiological importance during the MZT.
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Project description:Maternal mRNA degradation is a critical event of the maternal-to-zygotic transition (MZT) that determines the developmental potential of early embryos. Nuclear Poly(A)-binding proteins (PABPNs) are extensively involved in mRNA post-transcriptional regulation, but their function in the MZT has not been investigated. In this study, we find that the maternally exprressed PABPN1-like (PABPN1L), rather than its ubiquitously expressed homolog PABPN1, acts as an mRNA-binding adapter of the mammalian MZT licensing factor BTG4, which mediates maternal mRNA clearance. Female Pabpn1l null mice produce morphologically normal oocytes but are infertile owing to early developmental arrest of the resultant embryos at the 1-to-2-cell stage. Deletion of Pabpn1l impairs the deadenylation and degradation of a subset of BTG4-targeted maternal mRNAs during the MZT. In addition to recruiting BTG4 to the mRNA 3?-poly(A) tails, PABPN1L is also required for BTG4 protein accumulation in maturing oocytes by protecting BTG4 from SCF-?TrCP1 E3 ubiquitin ligase-mediated polyubiquitination and degradation. This study highlights a noncanonical cytoplasmic function of nuclear poly(A)-binding protein in mRNA turnover, as well as its physiological importance during the MZT.
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Project description:The Cytoplasmic mRNA Decay Landscape of Arabidopsis Seedlings
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Project description:Pumilio (PUM) is a Drosophila member of a conserved family of sequence-specific RNA-binding proteins that have been shown to regulate mRNA stability and/or translation in a variety of organisms. PUM has been shown to repress the translation of several mRNAs in the Drosophila early embryo; failure to repress these targets leads to lethal developmental defects. Here we use a combination of microarray-based gene expression profiling and next-generation sequencing to identify more than 200 mRNAs that are associated with full-length PUM protein in early embryos and to define a global role for PUM in mRNA decay. Surprisingly, despite the fact that PUM is maternally supplied and thus is present from the beginning of embryogenesis, the vast majority of PUM-directed decay occurs only after zygotic genome activation. We show that the smaug mRNA, which itself encodes an RNA-binding protein that directs transcript decay, is a direct target of PUM via binding sites in the smg 3'UTR. Whereas the endogenous smaug mRNA and the transgenic reporter mRNA that carries the smaug 3'UTR undergo decay after zygotic genome activation, a reporter with an array of PUM-binding sites decays before zygotic genome activation. These data support a model in which additional cis-elements in the smg 3'UTR delay decay until after zygotic genome activation.
2017-07-01 | GSE48645 | GEO
Project description:Cytoplasmic mRNA decay occurs through several pathways, but the contributions of these decay pathways to the degradation of specific mRNAs, and interactions between the pathways, are not well understood. We carried out a genome-wide analysis of mRNA decay rates using wild-type Arabidopsis and mutants with defects in mRNA decapping and SOV/DIS3L2. Decay rates and contributions of decapping and SOV to decay were estimated for 18,674 mRNAs using maximum likelihood modeling. Most mRNAs decayed by multiple pathways, few mRNAs degraded exclusively by mRNA decapping or SOV, and specific codon usage was linked to decay rates. Unexpected faster decay of transcripts in some genotypes was found to be independent of siRNAs; instead the data suggested an RNA buffering-like phenomenon in Arabidopsis, and that VCS (decapping) is essential for both this process and the decay of very unstable mRNAs.
2018-01-26 | GSE86359 | GEO
Project description:Cytoplasmic mRNA decay occurs through several pathways, but the contributions of these decay pathways to the degradation of specific mRNAs, and interactions between the pathways, are not well understood. We carried out a genome-wide analysis of mRNA decay rates using wild-type Arabidopsis and mutants with defects in mRNA decapping and SOV/DIS3L2. Decay rates and contributions of decapping and SOV to decay were estimated for 18,674 mRNAs using maximum likelihood modeling. Most mRNAs decayed by multiple pathways, few mRNAs degraded exclusively by mRNA decapping or SOV, and specific codon usage was linked to decay rates. Unexpected faster decay of transcripts in some genotypes was found to be independent of siRNAs; instead the data suggested an RNA buffering-like phenomenon in Arabidopsis, and that VCS (decapping) is essential for both this process and the decay of very unstable mRNAs.
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