A mechanism by which chromatin remodeling and m6A-mediated RNA regulation cooperate to suppress the precocious stability of key developmental regulators, thereby contributing to the establishment of the transcriptional program required for early embryo patterning in Arabidopsis is uncovered.
Abstract
N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes and is essential for Arabidopsis embryogenesis. However, how m6A mRNA methylation is coordinated with other regulatory pathways during development including embryogenesis remains largely unknown. Here, we report the SWI/SNF chromatin-remodeling subunit SWI3B as a bona fide interactor of the m6A methyltransferase MTA. Like m6A writer mutants, SWI3B is required for early embryo development. We demonstrate that the interaction between MTA and SWI3B is required for MTA function during embryogenesis. MTA and SWI3B are both required to establish the correct expression pattern of WOX8 and proper auxin maxima during early embryogenesis. Transcriptome analysis of isolated embryos from mta, swi3b, and fip37 mutants identified a shared set of upregulated transcripts, including STM as well as several NAC and ERF transcription factors that are normally absent or expressed at very low levels during early embryogenesis. Embryo-specific overexpression of ANAC087 and ERF114 genes phenocopied early embryonic defects observed in mta and swi3b mutants, indicating that their ectopic expression contributes to the observed developmental phenotype. Moreover, SWI3B and MTA are both required for m6A deposition on specific developmental transcripts. Together, our findings uncover a mechanism by which chromatin remodeling and m6A-mediated RNA regulation cooperate to suppress the precocious stability of key developmental regulators, thereby contributing to the establishment of the transcriptional program required for early embryo patterning in Arabidopsis. Highlights The SWI/SNF subunit SWI3B is a functional interactor of the m6A methyltransferase MTA during Arabidopsis embryogenesis SWI3B and MTA cooperate to establish embryo patterning, WOX8 expression, and auxin maxima MTA and SWI3B suppress precocious expression of STM, ANAC087 and ERF114 transcription factors that disrupt early embryo development SWI3B links chromatin-associated regulation with m6A-mediated control of transcript stability Graphical abstract
It is found that CNOT1 was upregulated during mammalian ZGA, and that its knockdown led to developmental arrest and a marked reduction in blastocyst formation, which indicates that CNOT1 is a potential YTHDF2 target that orchestrates maternal mRNA decay and ZGA during goat embryogenesis.
The RNA-binding proteins Musashi1 and Musashi2 (MSI1 and MSI2) regulate stem cell function and tissue plasticity by modulating mRNA translation. While typically known as translational repressors, the MSI1 and MSI2 proteins can also act as context-dependent activators of mRNA translation, although the mechanism of MSI-mediated translational activation is unknown. Here, we identify Embryonic Lethal Abnormal Vision-like (ELAVL) proteins as essential co-regulators of MSI1-dependent translational activation. In Xenopus laevis oocytes, antisense oligonucleotide knockdown of Elavl4 inhibited progesterone-stimulated maturation and blocked polyadenylation and translation of key MSI target mRNAs, including the Mos and Cyclin B5 mRNAs. Exogenous expression of ELAVL4 rescued these defects, confirming its necessity for maturation and cell cycle progression. Mechanistically, we determined that the ELAVL4 C-terminal domain interacts with the N-terminal RNA recognition motifs of MSI1 in an RNA-independent manner. Mass spectrometry and functional assays revealed this interaction is evolutionarily conserved: mouse ELAVL1 interacts with MSI1 in the pituitary, and human ELAVL1 rescues Elavl4-depleted Xenopus oocytes. Furthermore, knockdown of Elavl1 in a mammalian cell line abrogated MSI-dependent translational activation of a pituitary Prop1 3′ UTR mRNA reporter. Our results establish a conserved mechanism where ELAVL family members interact with MSI to promote MSI-dependent mRNA translational activation.
Katherine Bronson, Milla M. Reddick, Kenzie B. Macnicol et al.· Biomolecules· 0 citations
N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. ALKBH5 is an m6A demethylase that is essential for spermatogenesis. However, its function in meiotic prophase remains elusive. Here, we report that Alkbh5-knockout spermatocytes exhibit normal double-strand break (DSB) formation, homologous recombination and synapsis on autosomes but impaired synapsis between sex chromosomes. ALKBH5 depletion causes a significantly upregulated transcriptome on sex chromosomes and meiotic sex chromosome inactivation (MSCI) defects in spermatocytes at the pachytene stage. Mechanistically, ALKBH5 regulates SETDB1 expression in a post-transcriptional manner. Alkbh5 knockout inhibits SETDB1 protein expression, leading to the decreased SETDB1 signals on sex chromosomes and subsequently inhibiting H3K9me3 to form heterochromatin and silence transcriptional activity. Taken together, our findings identify ALKBH5 as a critical regulator of male meiosis by demonstrating that it is required to maintain proper SETDB1 protein levels, which in turn ensures the faithful execution of MSCI.
Qingqing Chen, Yu Xiang, Yang Song et al.· Communications Biology· 0 citations
Pentatricopeptide repeat (PPR) proteins are key regulators of the organellar RNA metabolism in plants. However, the functions of mitochondrial PPR proteins belonging to the subclass of P‐type PPR factors containing the SMR domain remain much less understood. Here, we characterize the EMBRYO DEFECTIVE 2217 (EMB2217/At1g79490), an essential PPR‐SMR factor in Arabidopsis thaliana. T‐DNA insertional lines at the AT1G79490 gene‐locus exhibit embryonic arrest at the late heart stage and display defective germination and seedling establishment. Partial complementation using an ABI3 promoter‐driven strategy enables efficient germination and the rescue of homozygous emb2217 plantlets. The pABI3::EMB2217 emb2217 −/− seedlings display severe growth defects due to impaired mitochondrial function, tightly associated with impaired OXPHOS activity. Analyses of mitochondrial RNA profiles reveal that EMB2217 is required for the processing of multiple group II introns that reside in the coding regions of several complex I (CI) subunits, the cox2 subunit of CIV, and the ribosomal rps3 factors. Our data further show that RNA maturation defects induce alternative electron transport and stress‐response pathways, which are associated with developmental defects and modulation of photosynthetic and cellular metabolic processes. Together, we identify EMB2217 as a general mitochondrial splicing factor whose loss compromises OXPHOS biogenesis and function, cellular energy supply, and plant development.
F. Marchetti, Nehuen Balestieri, Evelyn Becerra-Agudelo et al.· Physiologia Plantarum : An I...· 0 citations
N6-methyladenosine (m6A) is a vital epitranscriptomic modification that regulates plant development and stress responses. In rice (Oryza sativa L.), the identity of the catalytic subunit (MTA) of the core m6A writer complex has remained controversial because of inconsistent annotations based primarily on sequence homology. Here, phylogenetic analysis identified LOC_Os02g45110 as the putative catalytic subunit OsMTA, whereas LOC_Os01g16180 and LOC_Os03g05420 were classified as the structural subunits OsMTB1 and OsMTB2, respectively. All three proteins showed nuclear enrichment. Yeast two-hybrid, luciferase complementation imaging, and bimolecular fluorescence complementation assays demonstrated that OsMTA interacts independently with OsMTB1 and OsMTB2. Moreover, transient co-expression of OsMTA with either OsMTB1 or OsMTB2 increased global m6A levels in a heterologous system. No homozygous plants carrying frameshift mutations in OsMTA were obtained, suggesting that complete loss of OsMTA function is lethal. Knockdown of OsMTA or CRISPR/Cas9-mediated knockout of OsMTB1 and OsMTB2 significantly delayed heading date and reduced 1000-grain weight. Conversely, overexpressing OsMTA accelerated heading, whereas overexpressing OsMTB1 or OsMTB2 generally accelerated heading but significantly reduced 1000-grain weight. Together, these findings define the core composition of the rice m6A writer complex and reveal its effects on heading date and grain weight.
It is demonstrated that the RNA ac 4 C writer NAT10 is essential for the post-transcriptional regulation of mouse zygotic splicing activation and provide valuable view for further exploration of the epigenetic mechanism during maternal-to-zygotic transition.
Wen-Jing Wang, Yu-Ke Wu, Yun-Wen Wu et al.· Cell Death & Disease· 0 citations
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