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Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection

ABSTRACT: Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection

PROVIDER: PRJNA576915 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10259044_1.fastq.gz	Fastqsanger.gz
	SRR10259044_2.fastq.gz	Fastqsanger.gz
	SRR10259045_1.fastq.gz	Fastqsanger.gz
	SRR10259045_2.fastq.gz	Fastqsanger.gz
	SRR10259046_1.fastq.gz	Fastqsanger.gz

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Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection

Project description:The RNA modification N6-methyladenosine (m6A) can modulate mRNA fate and thus affect many biological processes. We analyzed m6A modification across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular transcripts, including RIOK3 and CIRBP. During viral infection, the addition of m6A to RIOK3 promotes its translation, while loss of m6A in CIRBP promotes alternative splicing. Importantly, we found that viral activation of innate immune sensing or the endoplasmic reticulum (ER) stress response contributes to the changes in m6A modification in RIOK3 and CIRBP, respectively. Further, several transcripts with infection-altered m6A profiles, including RIOK3 and CIRBP, encode proteins that influence DENV, ZIKV, and HCV infection. Overall, this work reveals that cellular signaling pathways activated during viral infection lead to alterations in m6A modification of host mRNAs to regulate infection.

2019-10-11 | GSE138730 | GEO

m6A modification of EBV transcripts

Project description:m6A modification of EBV transcripts

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Alphaherpesviruses remodel the cellular transcriptome to deplete m6A-containing transcripts

Project description:Virus infections are accompanied by major transcriptional changes in the host cell. We systematically investigated whether infection with viruses from different virus families specifically affects transcripts containing m6A, the most common internal modification of mRNA. Alphaherpesviruses were found to extensively alter m6A processing of infected cells.

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Altered m<sup>6</sup>A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection.

Project description:The RNA modification N6-methyladenosine (m6A) modulates mRNA fate and thus affects many biological processes. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular transcripts, including RIOK3 and CIRBP. During viral infection, the addition of m6A to RIOK3 promotes its translation, while loss of m6A in CIRBP promotes alternative splicing. Importantly, viral activation of innate immune sensing or the endoplasmic reticulum (ER) stress response contributes to the changes in m6A in RIOK3 or CIRBP, respectively. Further, several transcripts with infection-altered m6A profiles, including RIOK3 and CIRBP, encode proteins that influence DENV, ZIKV, and HCV infection. Overall, this work reveals that cellular signaling pathways activated during viral infection lead to alterations in m6A modification of host mRNAs to regulate infection.

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m6A RNA modification controls cell fate transition in mammalian embryonic stem cells

Project description:N6-methyl-adenosine (m6A) is the most abundant modification on messenger RNAs and is linked to human diseases, but its functions in mammalian development are poorly understood. Here we reveal the evolutionary conservation and function of m6A by mapping the m6A methylome in mouse and human embryonic stem cells. Thousands of messenger and long noncoding RNAs show conserved m6A modification, including transcripts encoding core pluripotency transcription factors. m6A is enriched over 3M-bM-^@M-^Y untranslated regions at defined sequence motifs, and marks unstable transcripts, including transcripts turned over upon differentiation. Genetic inactivation or depletion of mouse and human Mettl3, one of the m6A methylases, led to m6A erasure on select target genes, prolonged Nanog expression upon differentiation, and impaired ESCM-bM-^@M-^Ys exit from self-renewal towards differentiation into several lineages in vitro and in vivo. Thus, m6A is a mark of transcriptome flexibility required for stem cells to differentiate to specific lineages. Examing m6A modification differences in two different cell types

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Project description:Stress granules (SGs) are cytoplasmic structures that emerge in response to unfavorable environmental conditions. The mechanisms governing the accumulation of transcripts in SGs are only partially understood. Despite the recognized role of m6A in plant transcriptome regulation, its impact on SGs' composition and assembly remains elusive. In L. angustifolius, SGs display a distinctive bi-zonal structure comprising of a ring and a central area with differences in ultrastructure and composition. Subsequent to the transcriptome analysis, specific mRNA were chosen for investigating their localization within SGs and assessing m6A levels. Transcripts of hypoxia-responsive genes (ADH1 and HUP7) showed significantly lower levels of m6A compared to housekeeping genes, but only ADH1 was absent in SGs. HUP7 mRNA, characterized by a low quantity of m6A, is present both in the SGs and cytoplasm, probably due to extremely high expression level. The high amount of m6A was observed only during the assembly of SGs. In mutants of A. thaliana with reduced levels of m6A, ECT2 was not observed in SGs, and poly(A) RNA levels and the number of SGs were slightly reduced. In summary, our findings demonstrate a limited impact of m6A modification on SGs assembly. However, the interplay between m6A modification and the overall transcript quantity in the cytoplasm appears to play a regulatory role in mRNA partitioning and assembly of SGs

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Interplay between m6A modification and transcripts quantity: Impacts on mRNA composition in plant stress granules

Project description:Interplay between m6A modification and transcripts quantity: Impacts on mRNA composition in plant stress granules

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Project description:The modification N6-methyladenosine (m6A) affects rates of translation and degradation of mRNA transcripts. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV) using MeRIP-seq. We used the uninfected replicates, among which we would expect little biological variation in methylation, as negative controls to validate statistical methods for the detection of m6A changes in MeRIP-seq data. Applying validated statistical methods, we found that innate immune response to Flaviviridae viruses alters m6A modification of specific cellular transcripts compared to uninfected controls. Finally, we find that these changes in m6A can in turn affect splicing or translation of genes relevant to infection.

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Placental epitranscriptome-wide analysis of revealed the m6A modification level at 5’ UTR related fetal growth

Project description:To further understand the relationship between the level of gene expression and protein translation in human placenta, we focused on N6-methyladenosine: m6A, which is a methylation modification of mRNA acting as a post-transcriptional regulation which has drawn attention in recent years. It is said that m6A affects the fate of mRNA. In addition, it is thought that m6A affects gene expression in the placenta of preeclampsia which is a representative disease of perinatal period and fetal growth abnormality, and the placentas of children who were small for date (SFD) or heavy for date (HFD) were studied in addition to appropriate for date (AFD) preganancies. The SFD placentas contained half of the cases with PE. HEK293T cell was used to confirm the experimental system. PolyA RNA was purified from each tissue and cell, and libraries were prepared from immunoprecipitated (IP) samples using anti-m6A antibody and input samples, and sequenced with Hiseq 1500/2500 and RNAseq was carried out.

2019-10-10 | E-MTAB-6507 | biostudies-arrayexpress

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