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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

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			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

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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.

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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.

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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

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Ythdf

Project description:Drosophila melanogaster Ythdf, YTH N6-methyladenosine RNA binding protein, is differentially expressed in 16 experiment(s);

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Ythdf

Project description:Drosophila melanogaster Ythdf, YTH N6-methyladenosine RNA binding protein, is expressed in 5 baseline experiment(s);

| FBgn0039261 | ExpressionAtlas

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.

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Fmr1

Project description:Drosophila melanogaster Fmr1, Fmr1, is differentially expressed in 15 experiment(s);

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Fmr1

Project description:Drosophila melanogaster Fmr1, Fmr1, is expressed in 4 baseline experiment(s);

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