Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ythdf modulates Fmr1 target selection and restricts axonal growth in Drosophila

ABSTRACT: Ythdf modulates Fmr1 target selection and restricts axonal growth in Drosophila

PROVIDER: PRJNA679043 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13075739_1.fastq.gz	Fastqsanger.gz
	SRR13075739_2.fastq.gz	Fastqsanger.gz
	SRR13075740_1.fastq.gz	Fastqsanger.gz
	SRR13075740_2.fastq.gz	Fastqsanger.gz
	SRR13075741_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 54

Similar Datasets

Ythdf modulates Fmr1 target selection and restricts axonal growth in Drosophila

Project description:RIP-seq of Fmr1 in D. melanogaster whole brains.

2020-11-27 | GSE161655 | GEO

The m6A reader Ythdf restricts axonal growth in Drosophila through target selection modulation of the Fragile X mental retardation protein

Project description:The abundant mRNA modification N6-methyladenosine (m6A) regulates a variety of physiological processes through modulation of RNA metabolism. m6A is particularly enriched in the nervous system of several species and its dysregulation has been associated with neurodevelopmental defects as well as neural dysfunctions. In Drosophila, the loss of m6A alters fly behavior but the underlying mechanism and the role of m6A during nervous system development have remained elusive. Here we found that impairment of the m6A pathway leads to axonal overgrowth and misguidance at larval neuromuscular junctions as well as in the adult mushroom bodies. We identify the RNA binding protein Ythdf as the main m6A reader in the nervous system required for limiting axonal growth. Mechanistically, we show that Ythdf interacts directly with Fragile X mental retardation protein (Fmr1) to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m6A pathway controls development of the nervous system by modulating Fmr1 target selection.

2020-11-16 | GSE145342 | GEO

Ythdf is a N6-methyladenosine reader that modulates Fmr1 target mRNA selection and restricts axonal growth in Drosophila.

Project description:N6-methyladenosine (m6 A) regulates a variety of physiological processes through modulation of RNA metabolism. This modification is particularly enriched in the nervous system of several species, and its dysregulation has been associated with neurodevelopmental defects and neural dysfunctions. In Drosophila, loss of m6 A alters fly behavior, albeit the underlying molecular mechanism and the role of m6 A during nervous system development have remained elusive. Here we find that impairment of the m6 A pathway leads to axonal overgrowth and misguidance at larval neuromuscular junctions as well as in the adult mushroom bodies. We identify Ythdf as the main m6 A reader in the nervous system, being required to limit axonal growth. Mechanistically, we show that the m6 A reader Ythdf directly interacts with Fmr1, the fly homolog of Fragile X mental retardation RNA binding protein (FMRP), to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m6 A pathway controls development of the nervous system and modulates Fmr1 target transcript selection.

| S-EPMC7883056 | biostudies-literature

Ythdf is a N6-methyladenosine reader that modulates Fmr1 target mRNA selection and restricts axonal growth in Drosophila

Project description:N6-methyladenosine (m6A) regulates a variety of physiological processes through modulation of RNA metabolism. This modification is particularly enriched in the nervous system of several species, and its dysregulation has been associated with neurodevelopmental defects and neural dysfunctions. In Drosophila, loss of m6A alters fly behavior, albeit the underlying molecular mechanism and the role of m6A during nervous system development have remained elusive. Here we find that impairment of the m6A pathway leads to axonal overgrowth and misguidance at larval neuromuscular junctions as well as in the adult mushroom bodies. We identify Ythdf as the main m6A reader in the nervous system, being required to limit axonal growth. Mechanistically, we show that the m6A reader Ythdf directly interacts with Fmr1, the fly homolog of Fragile X mental retardation RNA binding protein (FMRP), to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m6A pathway controls development of the nervous system and modulates Fmr1 target transcript selection.

| S-SCDT-EMBOJ-2020-104975 | biostudies-other

The m6A reader Ythdf restricts axonal growth in Drosophila through target selection modulation of the Fragile X mental retardation protein

Project description:The m6A reader Ythdf restricts axonal growth in Drosophila through target selection modulation of the Fragile X mental retardation protein

| PRJNA606781 | ENA

ALBA proteins facilitate cytoplasmic YTHDF-mediated reading of m6A in plants

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

Uncovering the metabolic pleiotropy of FMR1-deficiency in Fragile X Syndrome

Project description:ene pleiotropy defines the capacity of a gene to impact multiple phenotypic characters. The Fragile X Mental Retardation 1 (FMR1) gene is a candidate for pleiotropy, as it controls protein synthesis through its product, the translational regulator FMRP. As FMR1 loss-of-function leads to neurodevelopmental defects and Fragile X Syndrome (FXS), intellectual disability and autism, FMR1 functions have been mostly studied in the brain. FMR1-deficiency could also have yet unexplored consequences in periphery and impact metabolism through translational repression in peripheral organs. We combined 1H NMR-based metabolic phenotyping and proteomics to reveal the pleiotropic metabolic effects associated with FMR1-deficiency in mouse and human. We demonstrate that Fmr1-deficiency in the mouse increases hepatic translation, improves glucose tolerance and insulin sensitivity and reduces adiposity, while enhancing -adrenergic driven lipolysis and utilization of lipid energetic substrates. Last, we provide converging evidences in FXS patients that the levels of glucose, insulin and free fatty acids are modified, suggesting that FMR1-deficiency also drives metabolic readjustments in human. As part of a larger study investigating the involvement of fmr in metabolic alteration in fmr1-KO mice, fmr1-KO mouse livers were analysed by MS.

2022-02-28 | PXD007241 | Pride

Dynamic O-GlcNAcylation of YTHDF proteins controls translation of m6A-modified mRNA

Project description:N6-methyladenosine (m6A) is the most abundant internal mRNA nucleotide modification in mammals, regulating critical aspects of cell physiology and differentiation. The YTHDF proteins are the primary readers of m6A modifications and exert physiological functions of m6A in the cytosol. Elucidating the regulatory mechanisms of YTHDF proteins is critical to understanding m6A biology. Here, we report a mechanism that protein post-translational modifications control the biological functions of the YTHDF proteins. We find that YTHDF1 and YTHDF3, but not YTHDF2, carry high levels of nutrient-sensing O-GlcNAc modifications. O-GlcNAc modification attenuates the translation promoting function of YTHDF1 and YTHDF3 by blocking their interactions with proteins associated with mRNA translation. We further demonstrate that O-GlcNAc modifications on YTHDF1 and YTHDF2 regulate the assembly, stability, and disassembly of stress granule, facilitating rapid exchange of m6A-modified mRNAs in stress granules for recovery from stress. Therefore, our results discover an important regulatory pathway of YTHDF functions, adding an additional layer of complexity to the post-transcriptional regulation function of mRNA m6A.

2023-08-31 | GSE216570 | GEO

Single-molecule analysis of RNA:protein interactions reveals sequential binding of different YTHDF proteins to the same mRNA molecules [Polysome]

Project description:N6-methyladenosine (m6A) plays critical roles in gene expression control by recruiting the cytoplasmic reader proteins YTHDF1,2 and 3. Recently, the function of YTHDF proteins and whether they bind to shared or distinct sets of methylated mRNAs in cells has been the subject of debate. Here, we developed TRIBE-STAMP, an approach for single-molecule detection of the target RNAs of two RNA binding proteins simultaneously in cells. Applying TRIBE-STAMP to the YTHDF proteins revealed that most target mRNAs are shared among the three YTHDF proteins. Surprisingly, we also found that individual mRNA molecules can be bound by more than one YTHDF protein throughout their lifetime. Furthermore, we show that YTHDF proteins bind sequentially to target methylated mRNAs, with YTHDF1 binding before YTHDF2 or YTHDF3. Our data reveal shared molecular interactions among the YTHDF proteins and support a model in which YTHDF1 and YTHDF3 are unlikely to promote rapid mRNA decay.

2022-10-28 | GSE201538 | GEO