The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. / Pinto, Rita; Vågbø, Cathrine B; Jakobsson, Magnus E; Kim, Yeji; Baltissen, Marijke P; O'Donohue, Marie-Françoise; Guzmán, Ulises H; Małecki, Jędrzej M; Wu, Jie; Kirpekar, Finn; Olsen, Jesper V; Gleizes, Pierre-Emmanuel; Vermeulen, Michiel; Leidel, Sebastian A; Slupphaug, Geir; Falnes, Pål Ø.

In: Nucleic Acids Research, Vol. 48, No. 2, 2020, p. 830-846.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pinto, R, Vågbø, CB, Jakobsson, ME, Kim, Y, Baltissen, MP, O'Donohue, M-F, Guzmán, UH, Małecki, JM, Wu, J, Kirpekar, F, Olsen, JV, Gleizes, P-E, Vermeulen, M, Leidel, SA, Slupphaug, G & Falnes, PØ 2020, 'The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA', Nucleic Acids Research, vol. 48, no. 2, pp. 830-846. https://doi.org/10.1093/nar/gkz1147

APA

Pinto, R., Vågbø, C. B., Jakobsson, M. E., Kim, Y., Baltissen, M. P., O'Donohue, M-F., Guzmán, U. H., Małecki, J. M., Wu, J., Kirpekar, F., Olsen, J. V., Gleizes, P-E., Vermeulen, M., Leidel, S. A., Slupphaug, G., & Falnes, P. Ø. (2020). The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. Nucleic Acids Research, 48(2), 830-846. https://doi.org/10.1093/nar/gkz1147

Vancouver

Pinto R, Vågbø CB, Jakobsson ME, Kim Y, Baltissen MP, O'Donohue M-F et al. The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. Nucleic Acids Research. 2020;48(2):830-846. https://doi.org/10.1093/nar/gkz1147

Author

Pinto, Rita ; Vågbø, Cathrine B ; Jakobsson, Magnus E ; Kim, Yeji ; Baltissen, Marijke P ; O'Donohue, Marie-Françoise ; Guzmán, Ulises H ; Małecki, Jędrzej M ; Wu, Jie ; Kirpekar, Finn ; Olsen, Jesper V ; Gleizes, Pierre-Emmanuel ; Vermeulen, Michiel ; Leidel, Sebastian A ; Slupphaug, Geir ; Falnes, Pål Ø. / The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. In: Nucleic Acids Research. 2020 ; Vol. 48, No. 2. pp. 830-846.

Bibtex

@article{fcb9de9d18e1453b9e9d0ae0f3c566df,
title = "The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA",
abstract = "RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem-loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.",
keywords = "Adenosine/analogs & derivatives, Catalysis, Humans, Methylation, Methyltransferases/chemistry, Protein Binding/genetics, RNA, Messenger/genetics, RNA, Ribosomal, 28S/chemistry",
author = "Rita Pinto and V{\aa}gb{\o}, {Cathrine B} and Jakobsson, {Magnus E} and Yeji Kim and Baltissen, {Marijke P} and Marie-Fran{\c c}oise O'Donohue and Guzm{\'a}n, {Ulises H} and Ma{\l}ecki, {J{\c e}drzej M} and Jie Wu and Finn Kirpekar and Olsen, {Jesper V} and Pierre-Emmanuel Gleizes and Michiel Vermeulen and Leidel, {Sebastian A} and Geir Slupphaug and Falnes, {P{\aa}l {\O}}",
year = "2020",
doi = "10.1093/nar/gkz1147",
language = "English",
volume = "48",
pages = "830--846",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA

AU - Pinto, Rita

AU - Vågbø, Cathrine B

AU - Jakobsson, Magnus E

AU - Kim, Yeji

AU - Baltissen, Marijke P

AU - O'Donohue, Marie-Françoise

AU - Guzmán, Ulises H

AU - Małecki, Jędrzej M

AU - Wu, Jie

AU - Kirpekar, Finn

AU - Olsen, Jesper V

AU - Gleizes, Pierre-Emmanuel

AU - Vermeulen, Michiel

AU - Leidel, Sebastian A

AU - Slupphaug, Geir

AU - Falnes, Pål Ø

PY - 2020

Y1 - 2020

N2 - RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem-loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.

AB - RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem-loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.

KW - Adenosine/analogs & derivatives

KW - Catalysis

KW - Humans

KW - Methylation

KW - Methyltransferases/chemistry

KW - Protein Binding/genetics

KW - RNA, Messenger/genetics

KW - RNA, Ribosomal, 28S/chemistry

U2 - 10.1093/nar/gkz1147

DO - 10.1093/nar/gkz1147

M3 - Journal article

C2 - 31799605

VL - 48

SP - 830

EP - 846

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 2

ER -

ID: 239210092