m6A RNA methylation promotes XIST-mediated transcriptional repression

Patil, Deepak P.; Chen, Chun-Kan; Pickering, Brian F.; Chow, Amy; Jackson, Constanza; Guttman, Mitchell; Jaffrey, Samie R.

doi:10.1038/nature19342

Cited by 1,440 publications

(1,799 citation statements)

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“…Recent findings from Jaffrey's lab showed that the abundant deposition of m 6 A is mediated by the methylation complex WTAP-METTL3, which is recruited to XIST-specific sites by RBM15 and RBM15B RNAbinding proteins (Patil et al, 2016). These findings reveal that this highly abundant post-transcriptional mark ensures YTHDC1 recruitment to at least a few of the methylated XIST residues and functionally enables the transcriptional repression effects of XIST on X chromosome genes.…”

Section: Introductionmentioning

confidence: 93%

“…Adenosine methylation m 6 A deposition in mRNA and miRNA: the story so far m 6 A is the most prevalent internal modification found in mRNA from viruses to mammals, but also occurs in small non-coding RNA (ncRNA) and long non-coding RNA (lncRNA) in many eukaryotic species (Patil et al, 2016;Yue et al, 2015). m 6 A is enriched at 3′ untranslated regions (UTRs) near stop codons, within long internal exons, in intergenic regions and introns and at 5′ UTRs ( Fig.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to other RNA species, the lncRNA X inactive specific transcript (XIST) is highly enriched in m 6 A residues, containing at least 78 throughout its length (Patil et al, 2016). Recent findings from Jaffrey's lab showed that the abundant deposition of m 6 A is mediated by the methylation complex WTAP-METTL3, which is recruited to XIST-specific sites by RBM15 and RBM15B RNAbinding proteins (Patil et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Post-transcriptional modifications in development and stem cells

Frye

Blanco

2016

Development

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Cells adapt to their environment by linking external stimuli to an intricate network of transcriptional, post-transcriptional and translational processes. Among these, mechanisms that couple environmental cues to the regulation of protein translation are not well understood. Chemical modifications of RNA allow rapid cellular responses to external stimuli by modulating a wide range of fundamental biochemical properties and processes, including the stability, splicing and translation of messenger RNA. In this Review, we focus on the occurrence of N 6 -methyladenosine (m 6 A), 5-methylcytosine (m 5 C) and pseudouridine (Ψ) in RNA, and describe how these RNA modifications are implicated in regulating pluripotency, stem cell self-renewal and fate specification. Both post-transcriptional modifications and the enzymes that catalyse them modulate stem cell differentiation pathways and are essential for normal development.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Post-transcriptional modifications in development and stem cells

Frye

Blanco

2016

Development

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“…40 XIST is m 6 A-methylated by METTL3, which is recruited to XIST through the proteins RBM15 and RBM15B. In an inducible XIST expression system, loss of METTL3 allows for induction of XIST, but its gene silencing function is impaired.…”

Section: Mrnamentioning

confidence: 99%

Publisher's Note

2017

RNA Biology

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RNA modifications have long been known to be central in the proper function of tRNA and rRNA. While chemical modifications in mRNA were discovered decades ago, their function has remained largely mysterious until recently. Using enrichment strategies coupled to next generation sequencing, multiple modifications have now been mapped on a transcriptome-wide scale in a variety of contexts. We now know that RNA modifications influence cell biology by many different mechanisms -by influencing RNA structure, by tuning interactions within the ribosome, and by recruiting specific binding proteins that intersect with other signaling pathways. They are also dynamic, changing in distribution or level in response to stresses such as heat shock and nutrient deprivation. Here, we provide an overview of recent themes that have emerged from the substantial progress that has been made in our understanding of chemical modifications across many major RNA classes in eukaryotes.

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“…Cap-independent translation initiation was enhanced by 5′ UTR methylation [47]. m A marks and impairs XIST-mediated gene silencing [49].…”

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confidence: 99%

Epitranscriptomics for Biomedical Discovery

Xiong¹,

Heruth²,

Jiang³

et al. 2017

Applications of RNA-Seq and Omics Strategies - From Microorganisms to Human Health

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Epitranscriptomics is a newly burgeoning ield pertaining to the complete delineation and elucidation of chemical modiications of nucleotides found within all classes of RNA that do not involve a change in the ribonucleotide sequence. More than 140 diverse and distinct nucleotide modiications have been identiied in RNA, dwaring the number of nucleotide modiications found in DNA. The majority of epitranscriptomic modiications have been identiied in ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA). However, in total, the knowledge of the occurrence, and speciically the function, of RNA modiications remains scarce. Recently, the rapid advancement of next-generation sequencing and mass spectrometry technologies have allowed for the identiication and functional characterization of nucleotide modiications in both protein-coding and non-coding RNA on a global, transcriptome scale. In this chapter, we will introduce the concepts of nucleotide modiication, summarize transcriptome-wide RNA modiication mapping techniques, highlight recent studies exploring the functions of RNA modiications and their association to disease, and inally ofer insight into the future progression of epitranscriptomics.

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m6A RNA methylation promotes XIST-mediated transcriptional repression

Cited by 1,440 publications

References 53 publications

Post-transcriptional modifications in development and stem cells

Post-transcriptional modifications in development and stem cells

Publisher's Note

Epitranscriptomics for Biomedical Discovery

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