The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

Magnus E. Jakobsson; Jędrzej M Małecki; Levon Halabelian; Benedikt S Nilges; Rita Pinto; Srikanth Kudithipudi; Stephanie Munk; Erna Davydova; Fawzi R Zuhairi; Cheryl H Arrowsmith; Albert Jeltsch; Sebastian A Leidel; Jesper V. Olsen; Pål Ø Falnes

doi:10.1038/s41467-018-05646-y

The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

Magnus E. Jakobsson, Jędrzej M Małecki, Levon Halabelian, Benedikt S Nilges, Rita Pinto, Srikanth Kudithipudi, Stephanie Munk, Erna Davydova, Fawzi R Zuhairi, Cheryl H Arrowsmith, Albert Jeltsch, Sebastian A Leidel, Jesper V. Olsen, Pål Ø Falnes

22 Citationer (Scopus)

65 Downloads (Pure)

Abstract

Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.

Originalsprog	Engelsk
Artikelnummer	3411
Tidsskrift	Nature Communications
Vol/bind	9
Udgave nummer	1
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-018-05646-y
Status	Udgivet - 1 dec. 2018

Adgang til dokumentet

10.1038/s41467-018-05646-y

The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation ratesForlagets udgivne version, 1,8 MB

Citationsformater

Jakobsson, M. E., Małecki, J. M., Halabelian, L., Nilges, B. S., Pinto, R., Kudithipudi, S., Munk, S., Davydova, E., Zuhairi, F. R., Arrowsmith, C. H., Jeltsch, A., Leidel, S. A., Olsen, J. V., & Falnes, P. Ø. (2018). The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates. Nature Communications, 9(1), Artikel 3411. https://doi.org/10.1038/s41467-018-05646-y

Jakobsson, ME, Małecki, JM, Halabelian, L, Nilges, BS, Pinto, R, Kudithipudi, S, Munk, S, Davydova, E, Zuhairi, FR, Arrowsmith, CH, Jeltsch, A, Leidel, SA, Olsen, JV & Falnes, PØ 2018, 'The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates', Nature Communications, bind 9, nr. 1, 3411. https://doi.org/10.1038/s41467-018-05646-y

@article{cd5faa04126a457d832052661d02591d,

title = "The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates",

abstract = "Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.",

author = "Jakobsson, {Magnus E.} and Ma{\l}ecki, {J{\c e}drzej M} and Levon Halabelian and Nilges, {Benedikt S} and Rita Pinto and Srikanth Kudithipudi and Stephanie Munk and Erna Davydova and Zuhairi, {Fawzi R} and Arrowsmith, {Cheryl H} and Albert Jeltsch and Leidel, {Sebastian A} and Olsen, {Jesper V.} and Falnes, {P{\aa}l {\O}}",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-05646-y",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

TY - JOUR

T1 - The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

AU - Jakobsson, Magnus E.

AU - Małecki, Jędrzej M

AU - Halabelian, Levon

AU - Nilges, Benedikt S

AU - Pinto, Rita

AU - Kudithipudi, Srikanth

AU - Munk, Stephanie

AU - Davydova, Erna

AU - Zuhairi, Fawzi R

AU - Arrowsmith, Cheryl H

AU - Jeltsch, Albert

AU - Leidel, Sebastian A

AU - Olsen, Jesper V.

AU - Falnes, Pål Ø

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.

AB - Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.

U2 - 10.1038/s41467-018-05646-y

DO - 10.1038/s41467-018-05646-y

M3 - Journal article

C2 - 30143613

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3411

ER -

The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater