The dynamic N1 -methyladenosine methylome in eukaryotic messenger RNA

Dan Dominissini; Sigrid Nachtergaele; Sharon Moshitch-Moshkovitz; Eyal Peer; Nitzan Kol; Moshe Shay Ben-Haim; Qing Dai; Ayelet Di Segni; Mali Salmon-Divon; Wesley C. Clark; Guanqun Zheng; Tao Pan; Oz Solomon; Eran Eyal; Vera Hershkovitz; Dali Han; Louis C. Doré; Ninette Amariglio; Gideon Rechavi; Chuan He

doi:10.1038/nature16998

The dynamic N¹ -methyladenosine methylome in eukaryotic messenger RNA

Dan Dominissini, Sigrid Nachtergaele, Sharon Moshitch-Moshkovitz, Eyal Peer, Nitzan Kol, Moshe Shay Ben-Haim, Qing Dai, Ayelet Di Segni, Mali Salmon-Divon, Wesley C. Clark, Guanqun Zheng, Tao Pan, Oz Solomon, Eran Eyal, Vera Hershkovitz, Dali Han, Louis C. Doré, Ninette Amariglio, Gideon Rechavi, Chuan He

Research output: Contribution to journal › Article › peer-review

732 Scopus citations

Abstract

Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N⁶ -methyladenosine (m⁶ A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N¹-methyladenosine (m¹ A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m¹ A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m¹ A in promoting translation of methylated mRNA.

Original language	English
Pages (from-to)	441-446
Number of pages	6
Journal	Nature
Volume	530
Issue number	7591
DOIs	https://doi.org/10.1038/nature16998
State	Published - 25 Feb 2016
Externally published	Yes

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Dominissini, D., Nachtergaele, S., Moshitch-Moshkovitz, S., Peer, E., Kol, N., Ben-Haim, M. S., Dai, Q., Di Segni, A., Salmon-Divon, M., Clark, W. C., Zheng, G., Pan, T., Solomon, O., Eyal, E., Hershkovitz, V., Han, D., Doré, L. C., Amariglio, N., Rechavi, G., & He, C. (2016). The dynamic N¹ -methyladenosine methylome in eukaryotic messenger RNA. Nature, 530(7591), 441-446. https://doi.org/10.1038/nature16998

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title = "The dynamic N1 -methyladenosine methylome in eukaryotic messenger RNA",

abstract = "Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N6 -methyladenosine (m6 A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1 A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m1 A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m1 A in promoting translation of methylated mRNA.",

author = "Dan Dominissini and Sigrid Nachtergaele and Sharon Moshitch-Moshkovitz and Eyal Peer and Nitzan Kol and Ben-Haim, {Moshe Shay} and Qing Dai and {Di Segni}, Ayelet and Mali Salmon-Divon and Clark, {Wesley C.} and Guanqun Zheng and Tao Pan and Oz Solomon and Eran Eyal and Vera Hershkovitz and Dali Han and Dor{\'e}, {Louis C.} and Ninette Amariglio and Gideon Rechavi and Chuan He",

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Dominissini, D, Nachtergaele, S, Moshitch-Moshkovitz, S, Peer, E, Kol, N, Ben-Haim, MS, Dai, Q, Di Segni, A, Salmon-Divon, M, Clark, WC, Zheng, G, Pan, T, Solomon, O, Eyal, E, Hershkovitz, V, Han, D, Doré, LC, Amariglio, N, Rechavi, G & He, C 2016, 'The dynamic N¹ -methyladenosine methylome in eukaryotic messenger RNA', Nature, vol. 530, no. 7591, pp. 441-446. https://doi.org/10.1038/nature16998

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AU - Dominissini, Dan

AU - Nachtergaele, Sigrid

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AU - Kol, Nitzan

AU - Ben-Haim, Moshe Shay

AU - Dai, Qing

AU - Di Segni, Ayelet

AU - Salmon-Divon, Mali

AU - Clark, Wesley C.

AU - Zheng, Guanqun

AU - Pan, Tao

AU - Solomon, Oz

AU - Eyal, Eran

AU - Hershkovitz, Vera

AU - Han, Dali

AU - Doré, Louis C.

AU - Amariglio, Ninette

AU - Rechavi, Gideon

AU - He, Chuan

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N2 - Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N6 -methyladenosine (m6 A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1 A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m1 A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m1 A in promoting translation of methylated mRNA.

AB - Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N6 -methyladenosine (m6 A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1 A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m1 A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m1 A in promoting translation of methylated mRNA.

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The dynamic N¹ -methyladenosine methylome in eukaryotic messenger RNA

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