Knockdown of YBX1 impairs alternative splicing and maternal mRNA decay during pre-implantation development
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ABSTRACT:
PROVIDER: PRJNA758279 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15652141_1.fastq.gz | Fastqsanger.gz | |||
| SRR15652141_2.fastq.gz | Fastqsanger.gz | |||
| SRR15652142_1.fastq.gz | Fastqsanger.gz | |||
| SRR15652142_2.fastq.gz | Fastqsanger.gz | |||
| SRR15652143_1.fastq.gz | Fastqsanger.gz |
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Project description:In mammals, maternal gene products decay and zygotic genome activation (ZGA) onsets during maternal to zygotic transition (MZT). Y-box binding protein YBX1 plays vital roles in RNA stabilization and transcriptional regulation, but its roles in pre-implantation development remain to be elucidated. In the present study, we aim to investigate the role of YBX1 during goat MZT and further explore the molecular mechanisms. The expression of YBX1 was increased during MZT in goat, bovine, human, and mice. We successfully knocked down YBX1 by microinjection of siRNA against YBX1, and the embryo development was impaired when YBX1 was knocked down. Using RNA-seq, we identified 1623 up-regulated and 3531 down-regulated genes in the 8-cell stage YBX1 knockdown embryos. GO/KEGG/GSEA enrichment analysis revealed that the down-regulated genes were enriched in regulation of RNA/mRNA stability and spliceosome, suggesting that YBX1 might medicate pre-implantation development by alternative splicing and maternal mRNA decay. To this end, we identified 3284 differential alternative splicing events and 1322 differentially expressed maternal mRNAs at the 8-cell stage YBX1 knockdown embryos compared to the controls. Moreover, the splicing factors and mRNA decay related genes were aberrantly expressed. Lastly, knockdown of YBX1 impaired transcriptional activity during ZGA in goat and mice as revealed by 5-EU staining. Our results identify that YBX1 serves an important role in maternal mRNA decay, alternative splicing, and the transcriptional activity required for early embryogenesis, which will broaden the current understanding of YBX1 functions during the stochastic reprogramming events.
2022-01-01 | GSE182908 | GEO
Project description:BackgroundIn mammals, maternal gene products decay and zygotic genome activation (ZGA) during maternal to zygotic transition (MZT) is critical for the early embryogenesis. Y-box binding protein YBX1 plays vital roles in RNA stabilization and transcriptional regulation, but its roles remain to be elucidated during pre-implantation development.MethodsIn the present study, we re-analyzed transcriptional level of YBX1 in mice, human, bovine, and goat embryos using public RNA-seq datasets. We further performed siRNA microinjection to knock down the expression of YBX1, and RNA sequencing of the 8-cell stage embryos in the control and YBX1 knockdown group. To reveal the regulation mechanisms of YBX1, we conducted differentially expression analysis, alternative splicing (AS) analysis, enrichment analysis, and 5-EU staining using DESeq2, rMATs, clusterProfiler, and immunofluorescence technique, respectively.ResultsThe expression of YBX1 was increased during MZT in goat, bovine, human, and mice, but significantly decreased in YBX1 knockdown embryos compared with the controls, suggesting successfully knockdown of YBX1. The percentage of blastocyst was decreased, while embryos blocked at the 2- and 4-cell stage were increased in YBX1 knockdown embryos compared to the controls. Using RNA-seq, we identified 1623 up-regulated and 3531 down-regulated genes in the 8-cell stage YBX1 knockdown embryos. Of note, the down-regulated genes were enriched in regulation of RNA/mRNA stability and spliceosome, suggesting that YBX1 might medicate RNA stability and AS. To this end, we identified 3284 differential AS events and 1322 differentially expressed maternal mRNAs at the 8-cell stage YBX1 knockdown embryos. Meanwhile, the splicing factors and mRNA decay-related genes showed aberrant expression, and the transcriptional activity during ZGA in goat and mice was compromised when YBX1 was knocked down.ConclusionYBX1 serves an important role in maternal mRNA decay, alternative splicing, and the transcriptional activity required for early embryogenesis, which will broaden the current understanding of YBX1 functions during the stochastic reprogramming events.
| S-EPMC8812265 | biostudies-literature
Project description:To study the function of zebrafish Ybx1 during early embryogenesis, we generated maternal ybx1 (Mybx1) mutant using CRISPR/Cas9 and report the transcriptome-wide changes in comparison to wild-type (WT) embryos. Our analysis reveals a dramatic loss of maternal mRNA decay and zygotic genome activation in Mybx1 embryos during maternal-to-zygotic transition.
2018-09-01 | GSE108924 | GEO
Project description:Chronic myeloid leukemia (CML) is a myeloproliferative disorder derived from hematopoietic stem cells (HSCs) that harbor Philadelphia chromosome (Ph chromosome). Leukemia stem cells (LSCs) in CML are insensitive to TKIs treatment, and are responsible for disease relapse. However, the molecular mechanisms for LSCs survival remains elusive. Here we show that YBX1 plays an important role in regulating survival of CML LSCs. We find that YBX1 expression is significantly increased in CML cells. Using CML patient-derived cell lines and a BCR-ABL-induced CML mouse model, we confirm that YBX1 is required for survival maintenance of LSCs. Deletion of YBX1 impairs the propagation of CML through impairing cell cycle and inducing apoptosis of LSCs. Mechanistically, we find that YBX1 regulates expression of apoptosis-related genes, and YBX1 binds MYC and BCL2 transcripts. YBX1 loss decreases expression of MYC and BCL2 by accelerating their mRNA decay. In addition, restoration of MYC and BCL2 efficiently rescue the defects of YBX1-deficient CML cells. Overall, our findings reveal a critical role of YBX1 in maintaining survival of CML LSCs, which may provide a rationale for targeting YBX1 in CML treatment.
2022-03-27 | GSE199304 | GEO
Project description:In order to identify YBX1 binding sites on endogenous RNA, we performed HITS-CLIP on endogenous YBX1 We used a previously published method to perform HITS-CLIP on endogenous YBX1 (Licatalosi D, et al. 2008, Nature 456:464-U22)
2015-05-08 | E-GEOD-63604 | biostudies-arrayexpress
Project description:In order to identify YBX1 binding sites on tRNA fragments, we performed small-RNA HITS-CLIP on endogenous YBX1 We used a previously published method to perform HITS-CLIP on endogenous YBX1 (Chi SW, et al. 2009, Nature 460:479)
2015-05-08 | E-GEOD-63597 | biostudies-arrayexpress
Project description:YBX1 is a multifunctional protein involved in the control of transcription and translation. We identified YBX1 as an target of MEK/ERK signaling in colorectal cancer cell lines. We performed a ChIP-chip analysis of HCT116 cells to identify new potential target genes of YBX1. Comparison of input DNA fragments with fragments coprecipitated with YBX1 in HCT116 cells.
2010-10-09 | E-GEOD-18337 | biostudies-arrayexpress
Project description:In order to identify YBX1-dependent targets that are modulated under hypoxic conditions, we used control and YBX1 knockdown cells grown under normoxia and hypoxia to profile gene expression levels. Control and YBX1-knockdown cells were grown and profiled under hypoxia and normoxia to identify YBX1-dependent hypoxia-induced target transcripts.
2015-05-08 | E-GEOD-63562 | biostudies-arrayexpress
Project description:Y box-binding protein 1 (Ybx1) is critical for embryogenesis and organogenesis. In zebrafish, we identify Ybx1 is predominantly expressed in the enterocytes of intestine in day5 larvae, whereas its immediately degradation driven by ubiquitination on day6. Here we show the maternal lethality with cardiac edema in ybx1-/- larvae, and postnatal larval lethality exhibited in ybx1-/- larvae within the death window from 10dpf to 20dpf. To study the underlying mechanisms for the ybx1-/- larvae partial lethality, we performed RNA-seq and experimental results showed the increased ROS might be the underlying cause for the postnatal lethality. By ascorbic acid treatment, we found ascorbic acid exposure prevented ybx1-/- larvae from postnatal lethality, while hydrogen peroxide aggravated ybx1-/- larvae postnatal lethality during the death window. By RNA-seq analysis, we also found significantly increased expressions of mmp9 and mmp13a in ybx1-/- larvae, and by inhibition of either MMP9 or MMP13a expression partially rescue the ybx1-/- postnatal lethality during the death window. Later, we further identify the intestinal impairs on 30 dpf and further deteriorated severe intestinal disorder in Ybx1 deficiency zebrafish. By exposure of ybx1-/- zebrafish for 14 days, we discover ascorbic acid partially mend the impaired intestine in ybx1-/-. In this study, we demonstrate that ybx1-/- larvae were ROS-susceptible, and the increased inflammation in ybx1-/- larvae intestine identified enables the ybx1-/- zebrafish as good model for studying of intestinal disease.
2020-12-15 | GSE134334 | GEO
Project description:In order to identify YBX1-dependent targets that are modulated upon changing the levels of endogenous tRFs, we used transient transfection of antisense locked-nucleic acids (LNAs) against tRFAsp, tRFGly, tRFGlu, and tRFTyr followed by microarray profiling. Synthetic antisense locked-nucleic acids (LNAs) targeting the YBX1 binding site on tRFAsp, tRFGly, tRFGlu, and tRFTyr were transfected into control and YBX1-knockdown cells to identify YBX1-dependent targets that are modulated due to tRF loss-of-function.
2015-05-08 | E-GEOD-63564 | biostudies-arrayexpress