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Ythdf m6A readers compensate each other in a context dependent manner [eCLIP]

ABSTRACT: Ythdf m6A readers compensate each other in a context dependent manner [eCLIP]

PROVIDER: PRJNA637256 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11923227.fastq.gz	Fastqsanger.gz
	SRR11923228.fastq.gz	Fastqsanger.gz
	SRR11923229.fastq.gz	Fastqsanger.gz
	SRR11923230.fastq.gz	Fastqsanger.gz
	SRR11923231.fastq.gz	Fastqsanger.gz

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Ythdf m6A readers compensate each other in a context dependent manner

Project description:Ythdf m6A readers compensate each other in a context dependent manner

| PRJNA622932 | ENA

Ythdf m6A readers compensate each other in a context dependent manner [RNA-seq]

Project description:Ythdf m6A readers compensate each other in a context dependent manner [RNA-seq]

| PRJNA622277 | ENA

Ythdf m6A readers compensate each other in a context dependent manner [Ribo-seq]

Project description:Ythdf m6A readers compensate each other in a context dependent manner [Ribo-seq]

| PRJNA624906 | ENA

Ythdf m6A readers compensate each other in a context dependent manner [3'UTR RNA-seq]

Project description:Ythdf m6A readers compensate each other in a context dependent manner [3'UTR RNA-seq]

| PRJNA622947 | ENA

Ythdf m6A readers compensate each other in a context dependent manner [eCLIP]

Project description:YTH domain family proteins Ythdf1, Ythdf2, Ythdf3 are three readers with highly similar structure, which were shown to have different roles in the cell. However, their similarity and the fact that they tend to bind the same targets suggest that in some cases they may have an overlapping role. In this paper, we systematically knocked-out (KO) each of the three readers and the three together (triple-KO), and estimated the effect in-vitro in mouse embryonic stem cells (mESCs), and in-vivo, in viability and gametogenesis. We show that in mESCs there is a compensation between the three readers, with a dramatic hyper-pluripotent phenotype only in the triple-KO. However, in-vivo, Ythdf2 has a dominant role that cannot be compensated by Ythdf1 or Ythdf3, both in viability of the mouse pups and in gametogenesis. We suggest that compensation is dosage-dependent, and in-vivo we cannot detect it due to difference in the readers’ expression, both in level and in spatial location. In addition, we found that Ythdf1 and Ythdf3 specifically down-regulate 2-cell genes, that Ythdf2-KO in gametogenesis affects microtubuline related genes, and that Mettl3-KO severity is increased as the deletion occurs earlier in gametogenesis.

2020-06-04 | GSE151788 | GEO

Ythdf m6A readers compensate each other in a context dependent manner [Ribo-seq]

2020-06-04 | GSE148536 | GEO

Ythdf m6A readers compensate each other in a context dependent manner [RNA-seq]

2020-06-04 | GSE147849 | GEO

Ythdf m6A readers compensate each other in a context dependent manner [3'UTR RNA-seq]

2020-06-04 | GSE148038 | GEO

Ythdf m6A readers compensate each other in a context dependent manner

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-04 | GSE148039 | GEO

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

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