Nm-seq maps 2′-O-methylation sites in human mRNA with base precision

Dai, Qing; Moshitch-Moshkovitz, Sharon; Han, Dali; Kol, Nitzan; Amariglio, Ninette; Rechavi, Gideon; Dominissini, Dan; He, Chuan

doi:10.1038/nmeth.4294

Cited by 223 publications

(242 citation statements)

References 37 publications

Supporting

Mentioning

236

Contrasting

Order By: Relevance

“…Nm-seq uncovered over 7,000 potential methylation sites in human mRNA revealing a consensus sequence and enrichment within three amino acid codons and extensive ribose methylation in all four bases. The same approach has been used to map these sites in rRNA (Dai et al, 2017; Zhu et al, 2017). …”

Section: Ribose Modificationmentioning

confidence: 99%

“…In vivo , 2’-OMe is typically found in unstructured CDS regions of mRNA, with half of all sites falling within 50 nucleotides of the nearest splice site, suggesting a link between structural elements and mRNA processing outcomes. Interestingly, 2’-OMe sites concentrate to six codons that encode three amino acids: glutamate, lysine, and glutamine, perhaps dependent on the RNA-binding properties of specific methyltransferase (Dai et al, 2017). This suggests that 2’-OMe in mRNA may affect translation efficiency, a concept that has been demonstrated in modified bacterial mRNA (Hoernes et al, 2016).…”

Section: Properties Of Mrna Modifications – Structure and Functionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic RNA Modifications in Gene Expression Regulation

Roundtree

Evans

Pan

et al. 2017

Cell

Self Cite

2,324

2,401

View full text Add to dashboard Cite

Over one hundred types of chemical modifications have been identified in cellular RNAs. While the 5’ cap modification and the poly(A) tail of eukaryotic messenger RNA play key roles in regulation, internal modifications are gaining attention for their roles in mRNA metabolism. The most abundant internal modification is N6-methyladenosine (m6A), and identification of proteins that install, recognize, and remove this and other marks have revealed roles for mRNA modification in nearly every aspect of the mRNA lifecycle, as well as in various cellular, developmental, and disease processes. Abundant noncoding RNAs such as transfer RNAs, ribosomal RNAs and spliceosomal RNAs are also heavily modified and depend on the modifications for their biogenesis and function. Our understanding of the biological contributions of these different chemical modifications is beginning to take shape, but it’s clear that in both coding and noncoding RNA, dynamic modifications represent a new layer of control of genetic information.

show abstract

Section: Ribose Modificationmentioning

confidence: 99%

Section: Properties Of Mrna Modifications – Structure and Functionmentioning

confidence: 99%

Dynamic RNA Modifications in Gene Expression Regulation

Roundtree

Evans

Pan

et al. 2017

Cell

Self Cite

2,324

2,401

View full text Add to dashboard Cite

show abstract

“…The m 6 A-mapping concept was quickly applied to other modified nucleotides, resulting in transcriptome-wide maps of N 6 ,2 0 -O-dimethyladenosine (m 6 A m ) [10], 5-methylcytidine (m 5 C) [11][12][13], pseudouridine [14][15][16], 5-hydroxymethylcytidine (hm 5 C) [17], 2 0 -O-methylated nucleotides (N m ) [18], and N 1 -methyladenosine (m 1 A) [19,20]. The m 6 A-mapping concept was quickly applied to other modified nucleotides, resulting in transcriptome-wide maps of N 6 ,2 0 -O-dimethyladenosine (m 6 A m ) [10], 5-methylcytidine (m 5 C) [11][12][13], pseudouridine [14][15][16], 5-hydroxymethylcytidine (hm 5 C) [17], 2 0 -O-methylated nucleotides (N m ) [18], and N 1 -methyladenosine (m 1 A) [19,20].…”

Section: Epitranscriptomic Regulation Of Mrnamentioning

confidence: 99%

FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications

2018

View full text Add to dashboard Cite

The fate of mRNA is regulated by epitranscriptomic nucleotide modifications, the most abundant of which is N -methyladenosine (m A). Although the pattern and distribution of m A in mRNA is mediated by specific methyltransferases, a recent hypothesis is that specific demethylases or 'erasers' allow m A to be dynamically reversed by signaling pathways. In this Review, we discuss the data in support and against this model. New insights into the function of fat mass and obesity-associated protein (FTO), the original enzyme thought to be an m A eraser, reveal that its physiologic target is not m A, but instead is N ,2'-O-dimethyladenosine (m A ). Another m A demethylase, ALKBH5, appears to have functions limited to sperm development in normal mice. Overall, the majority of the data suggest that m A is generally not reversible, although m A may be susceptible to demethylation in pathophysiological states such as cancer.

show abstract

“…Although m 6 A and pseudouridine are well-documented epi transcriptomic modifications, and their mapping can be performed reliably 10,11 , the validity of newer modification maps is unclear, because the modifications were mapped from sequencing data but not biochemically validated. A recent study 12 of the mammalian transcriptome mapped approximately 3,500 nucleotides that contain methyl groups on the ribose part of the molecules. However, subsequent reanalysis showed that the key sequence motifs discovered in this study matched those of 'primer' sequences used to generate complementary DNA, a common sequencing artefact 13 .…”

Section: Years Agomentioning

confidence: 99%

Shrinking maps of RNA modifications

Grozhik

Jaffrey

2017

Nature

View full text Add to dashboard Cite

California, and seemed to be an ordinary supernova already well under way. It was infrequently observed over the next few months, and was eventually classified 4 as a common type of supernova called type II-P in January 2015. Its subsequent failure to decline led Arcavi and colleagues to flag it for special attention.Not only did iPTF14hls not fade, but as months stretched into years, the authors found that its brightness varied by as much as 50% on an irregular timescale, as if it were exploding again and again. Although not among the most luminous supernovae ever seen, iPTF14hls was brighter than an ordinary type II-P explosion and, by lasting so long, it radiated much more energy.Just as the light from iPTF14hls refused to fade, the spectrum of the light refused to evolve. Usually, as a supernova expands, it reveals deeper, more-slowly moving material, and the lines in its spectrum get narrower. But in the case of iPTF14hls, Arcavi et al. found that the light-emitting region maintained the same speed throughout the supernova's lifetime.This result might make sense if the authors had observed the emission from a single shell of ejected matter. However, the radius of such a shell would have increased over time. Radiation theory tells us that if something gets bigger but maintains its luminosity, it should also get cooler. Confounding expectations again, iPTF14hls remained at the same temperature (about 6,000 kelvin), suggesting that the radius of the light-emitting region was roughly constant. What was going on?Supernovae shine for one of four reasons 5 : radioactive decay; radiation released by the shock-heated envelope of a massive star as it expands and cools (ordinary type II-P supernovae); colliding shells that convert kinetic energy into light (type IIn supernovae); or radiation from a central, compact stellar object such as a magnetar. In the case of iPTF14hls, radioactivity can be ruled out because the isotopes that have the correct lifetime to explain the emission are not sufficiently abundant in the explosion. Likewise, radiation from a shock-heated envelope would require an envelope mass and an explosion energy that are incompatible with our understanding of stellar evolution.It therefore falls to a magnetar or colliding shells to explain iPTF14hls. Arcavi and colleagues explore both possibilities and rule out the simplest models. Using standard formulae, which might not be adequate for this event, they conclude that the initial luminosity of a magnetar would be too high to explain their observations. Similarly, the colliding shells that are typical of type IIn supernovae would produce X-ray and radio emission that was not seen for iPTF14hls, and narrower spectral lines than were observed.Having ruled out all of the standard theoretical models, Arcavi et al. tie their hopes to an alternative scenario: a pulsational pairinstability supernova 6 . In this model, during the death of an extremely massive star, violent thermonuclear instabilities in the final stages of nuclear fusion lead to repeated su...

show abstract

Nm-seq maps 2′-O-methylation sites in human mRNA with base precision

Cited by 223 publications

References 37 publications

Dynamic RNA Modifications in Gene Expression Regulation

Dynamic RNA Modifications in Gene Expression Regulation

FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications

Shrinking maps of RNA modifications

Contact Info

Product

Resources

About

Nm-seq maps 2′-O-methylation sites in human mRNA with base precision

Cited by 223 publications

References 37 publications

Dynamic RNA Modifications in Gene Expression Regulation

Dynamic RNA Modifications in Gene Expression Regulation

FTO, m6Am, and the hypothesis of reversible epitranscriptomic mRNA modifications

Shrinking maps of RNA modifications

Contact Info

Product

Resources

About

FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications