M6A controls neurogenesis and sex determination in Drosophila via its nuclear reader protein YT521-B
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ABSTRACT:
PROVIDER: PRJNA315419 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3231880_1.fastq.gz | Fastqsanger.gz | |||
| SRR3231880_2.fastq.gz | Fastqsanger.gz | |||
| SRR3231980_1.fastq.gz | Fastqsanger.gz | |||
| SRR3231980_2.fastq.gz | Fastqsanger.gz | |||
| SRR3231990_1.fastq.gz | Fastqsanger.gz |
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Project description:N6-methyladenosine RNA (m6A) is the most abundant internal mRNA modification in mammals. While its role in the regulation of posttranscriptional gene expression is beginning to be unveiled, its function during development of complex organisms is poorly understood. Here, we identify Spenito as a novel member of the methyltransferase complex and show that m6A in Drosophila is necessary for proper synaptic growth, and in regulation of early steps of pre-mRNA splicing. Splicing of Sex-lethal and of its downstream targets are defective in animals lacking m6A, revealing also important roles in sex determination and dosage compensation. Finally, we implicate the nuclear m6A reader protein, YT521-B, as a crucial effector of m6A modifications in vivo. Altogether, our work provides important novel insights into m6A biology through identification and characterization of both m6A-writing and -reading proteins in Drosophila and their effects on splicing, neurogenesis and sex-determination within the context of the whole animal.
2016-12-07 | GSE79289 | GEO
Project description:N6-methyladenosine RNA (m6A) is the most abundant internal mRNA modification in mammals. While its role in the regulation of posttranscriptional gene expression is beginning to be unveiled, its function during development of complex organisms is poorly understood. Here, we identify Spenito as a novel member of the methyltransferase complex and show that m6A in Drosophila is necessary for proper synaptic growth, and in regulation of early steps of pre-mRNA splicing. Splicing of Sex-lethal and of its downstream targets are defective in animals lacking m6A, revealing also important roles in sex determination and dosage compensation. Finally, we implicate the nuclear m6A reader protein, YT521-B, as a crucial effector of m6A modifications in vivo. Altogether, our work provides important novel insights into m6A biology through identification and characterization of both m6A-writing and -reading proteins in Drosophila and their effects on splicing, neurogenesis and sex-determination within the context of the whole animal.
2016-12-07 | GSE86276 | GEO
Project description:N6-methyladenosine RNA (m6A) is the most abundant internal mRNA modification in mammals. While its role in the regulation of posttranscriptional gene expression is beginning to be unveiled, its function during development of complex organisms is poorly understood. Here, we identify Spenito as a novel member of the methyltransferase complex and show that m6A in Drosophila is necessary for proper synaptic growth, and in regulation of early steps of pre-mRNA splicing. Splicing of Sex-lethal and of its downstream targets are defective in animals lacking m6A, revealing also important roles in sex determination and dosage compensation. Finally, we implicate the nuclear m6A reader protein, YT521-B, as a crucial effector of m6A modifications in vivo. Altogether, our work provides important novel insights into m6A biology through identification and characterization of both m6A-writing and -reading proteins in Drosophila and their effects on splicing, neurogenesis and sex-determination within the context of the whole animal.
2016-12-07 | GSE79296 | GEO
Project description:N6-methyladenosine RNA (m6A) is the most abundant internal mRNA modification in mammals. While its role in the regulation of posttranscriptional gene expression is beginning to be unveiled, its function during development of complex organisms is poorly understood. Here, we identify Spenito as a novel member of the methyltransferase complex and show that m6A in Drosophila is necessary for proper synaptic growth, and in regulation of early steps of pre-mRNA splicing. Splicing of Sex-lethal and of its downstream targets are defective in animals lacking m6A, revealing also important roles in sex determination and dosage compensation. Finally, we implicate the nuclear m6A reader protein, YT521-B, as a crucial effector of m6A modifications in vivo. Altogether, our work provides important novel insights into m6A biology through identification and characterization of both m6A-writing and -reading proteins in Drosophila and their effects on splicing, neurogenesis and sex-determination within the context of the whole animal.
2016-12-07 | GSE79295 | GEO
Project description:N6-methyladenosine (m6A) has recently emerged as a widespread and conserved RNA modification that modulates messenger RNA (mRNA) processing and activity. As most m6A studies have been conducted in cultured cells, we established Drosophila as a model system that combines molecular and genomic analyses of m6A with investigations of organismal biology. We first apply miCLIP sequencing to map m6A modifications at single-nucleotide resolution during Drosophila embryogenesis. We next characterize Drosophila components of the m6A "writer" methyltransferase complex [MTC factors, METTL3/IME4, METTL14, FL(2)D and Nito], and characterize m6A-binding properties of the YTH domain-containing proteins, YT521-B and CG6422. We complement this by generating a collection of mutants in m6A writer and reader components. While Drosophila orthologs of mammalian MTC factors that have additional roles in splicing are lethal, our mutants in METTL and YTH factors are viable but present specific developmental and behavioral defects. We note that several mammalian m6A factors were originally identified as Drosophila regulators of Sxl splicing, which generates the master determinant of female identity. While our mutants in dedicated writer and reader machinery are not required to accumulate Sxl protein in the ovary, maternal loss of m6A writers and readers collaborates with reduction of Sxl to induce female lethality. Our data indicate Sxl is directly regulated by the m6A pathway, since miCLIP data show Sxl is a substantial target of intronic m6A in early embryos, in addition to bearing exonic m6A. Consistent with this, female-specific Sxl splicing is defective in m6A pathway mutants. YT521-B appears to be the major effector of m6A for Sxl regulation, as it shows much stronger genetic interactions with Sxl than CG6422 and YT521-B overexpression can induce female-specific Sxl splicing. Overall, our transcriptomic and genetic toolkit for studying the m6A pathway in Drosophila reveals a major biological utilization in establishing sex-specific splicing.
2017-04-22 | GSE97004 | GEO
Project description:The N6-methyladenosine (m6A) is the most abundant internal modification in almost all eukaryotic messenger RNAs, and is dynamically regulated. Therefore, identification of m6A readers is especially important in determining the cellular function of m6A. YTHDF2 has recently been characterized as the first m6A reader that regulates the cytoplasmic stability of methylated RNA. Here we show that YTHDC1 is a nuclear m6A reader and report the crystal structure of the YTH domain of YTHDC1 bound to m6A-containing RNA. We further determined the structure of another YTH domain, YTHDF1, and found that the YTH domain utilizes a conserved aromatic cage to specifically recognize the methyl group of m6A. Our structural characterizations of the YTHDC1-m6A RNA complex also shed light on the molecular basis for the preferential binding of the GG(m6A)C sequence by YTHDC1 and confirm the YTH domain as a specific m6A RNA reader. PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) was applied to human YTHDC1 protein to identify its binding sites.
2014-09-18 | E-GEOD-58352 | biostudies-arrayexpress
Project description:The RNA modification N6-methyladenosine (m6A) has critical roles in many biological processes. However, the function of m6A in the early phase of mammalian development remains poorly understood. Here we show that the m6A reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an m6A-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target m6A RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for m6A RNA and YTHDC1 in chromatin modification and retrotransposon repression. This SuperSeries is composed of the SubSeries listed below.
2021-01-24 | GSE146467 | GEO
Project description:N6-methyladenosine (m6A) exerts many of its regulatory effects on eukaryotic mRNAs by recruiting cytoplasmic YT521-B homology domain family (YTHDF) proteins. Here, we show that in Arabidopsis, the interaction between m6A and the major YTHDF protein ECT2 also involves the mRNA-binding ALBA protein family. ALBA and YTHDF proteins physically associate via a deeply conserved short linear motif in the intrinsically disordered region of YTHDF proteins, their mRNA targets overlap, and ALBA4 binding sites are juxtaposed to m6A sites. These binding sites correspond to pyrimidine-rich elements previously found to be important for m6A binding of ECT2. Accordingly, both biological effects of ECT2 and its binding to m6A targets in vivo require ALBA association. Our results introduce the YTHDF-ALBA complex as the functional cytoplasmic m6A-reader in plants and define a molecular foundation for the concept of facilitated m6A reading that increases the potential for combinatorial control of biological m6A effects.
2024-11-18 | PXD052232 | Pride
Project description:The N6-methyladenosine (m6A) is the most abundant internal modification in almost all eukaryotic messenger RNAs, and is dynamically regulated. Therefore, identification of m6A readers is especially important in determining the cellular function of m6A. YTHDF2 has recently been characterized as the first m6A reader that regulates the cytoplasmic stability of methylated RNA. Here we show that YTHDC1 is a nuclear m6A reader and report the crystal structure of the YTH domain of YTHDC1 bound to m6A-containing RNA. We further determined the structure of another YTH domain, YTHDF1, and found that the YTH domain utilizes a conserved aromatic cage to specifically recognize the methyl group of m6A. Our structural characterizations of the YTHDC1-m6A RNA complex also shed light on the molecular basis for the preferential binding of the GG(m6A)C sequence by YTHDC1 and confirm the YTH domain as a specific m6A RNA reader.
2014-09-18 | GSE58352 | GEO
Project description:m6A controls neurogenesis and sex determination in Drosophila via its nuclear reader protein YT521-B [RNA-Seq, heads]
| PRJNA315417 | ENA