Saito et al. 2022 (PRJNA789247)

General Details

Title RNA-seq and Ribo-seq of Ythdc2KO and Ythdc2-WLA mutants
Organism
Number of Samples 12
Release Date 2021/12/15 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP350895
ENA SRP350895
GEO GSE190980
BioProject PRJNA789247

Publication

Title
Authors Saito Y, Hawley BR, Puno MR, Sarathy SN, Lima CD, Jaffrey SR, Darnell RB, Keeney S, Jain D
Journal Genes & development
Publication Date 2022 Feb 1
Abstract Mechanisms regulating meiotic progression in mammals are poorly understood. The N 6 -methyladenosine (m 6 A) reader and 3' → 5' RNA helicase YTHDC2 switches cells from mitotic to meiotic gene expression programs and is essential for meiotic entry, but how this critical cell fate change is accomplished is unknown. Here, we provide insight into its mechanism and implicate YTHDC2 in having a broad role in gene regulation during multiple meiotic stages. Unexpectedly, mutation of the m 6 A-binding pocket of YTHDC2 had no detectable effect on gametogenesis and mouse fertility, suggesting that YTHDC2 function is m 6 A-independent. Supporting this conclusion, CLIP data defined YTHDC2-binding sites on mRNA as U-rich and UG-rich motif-containing regions within 3' UTRs and coding sequences, distinct from the sites that contain m 6 A during spermatogenesis. Complete loss of YTHDC2 during meiotic entry did not substantially alter translation of its mRNA binding targets in whole-testis ribosome profiling assays but did modestly affect their steady-state levels. Mutation of the ATPase motif in the helicase domain of YTHDC2 did not affect meiotic entry, but it blocked meiotic prophase I progression, causing sterility. Our findings inform a model in which YTHDC2 binds transcripts independent of m 6 A status and regulates gene expression during multiple stages of meiosis by distinct mechanisms. © 2022 Saito et al.; Published by Cold Spring Harbor Laboratory Press.
PMC PMC8887132
PMID 35058317
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR17238161 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238160 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238159 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238158 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238157 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238156 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238155 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238154 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238153 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238152 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238151 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
SRR17238150 PRJNA789247 Mus musculus 0.0 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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