. Cnrs-atip-avenir and . Program, the Agence Nationale pour la Recherche

E. Cnrs and . Polytechnique,

. Cnrs-pics-program, pics

. Ulb;-région-wallonne,

, ); National Institutes of Health, J.L

D. Forschungsgemeinschaft,

A. Ben-shem, L. Jenner, G. Yusupova, and M. Yusupov, Crystal Structure of the Eukaryotic Ribosome, Science, vol.330, issue.6008, pp.1203-1209, 2010.

K. E. Bohnsack and M. T. Bohnsack, Uncovering the assembly pathway of human ribosomes and its emerging links to disease, EMBO J, vol.38, p.100278, 2019.

J. Bassler and E. Hurt, Eukaryotic ribosome assembly, Annu. Rev. Biochem, vol.88, 2018.

S. Klinge and J. L. Woolford, Ribosome assembly coming into focus, Nat. Rev. Mol. Cell Biol, vol.20, pp.116-131, 2019.

A. Aspesi and S. R. Ellis, Rare ribosomopathies: insights into mechanisms of cancer, Nat. Rev. Cancer, vol.19, pp.228-238, 2019.

J. Pelletier, G. Thomas, and S. Volarevic, Ribosome biogenesis in cancer: new players and therapeutic avenues, Nat. Rev. Cancer, vol.18, pp.51-63, 2018.

D. L. Lafontaine, Noncoding RNAs in eukaryotic ribosome biogenesis and function, Nature Structural & Molecular Biology, vol.22, issue.1, pp.11-19, 2015.

J. Erales, V. Marchand, B. Panthu, S. Gillot, S. Belin et al., Evidence for rRNA 2?-O-methylation plasticity: Control of intrinsic translational capabilities of human ribosomes, Proceedings of the National Academy of Sciences, vol.114, issue.49, pp.12934-12939, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02191312

S. Sharma, V. Marchand, Y. Motorin, and D. L. Lafontaine, Identification of sites of 2?-O-methylation vulnerability in human ribosomal RNAs by systematic mapping, Scientific Reports, vol.7, issue.1, p.11490, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01799319

M. Taoka, Y. Nobe, Y. Yamaki, K. Sato, H. Ishikawa et al., Landscape of the complete RNA chemical modifications in the human 80S ribosome, Nucleic Acids Research, vol.46, issue.18, pp.9289-9298, 2018.

S. K. Natchiar, A. G. Myasnikov, H. Kratzat, I. Hazemann, and B. P. Klaholz, Visualization of chemical modifications in the human 80S ribosome structure, Nature, vol.551, issue.7681, pp.472-477, 2017.
URL : https://hal.archives-ouvertes.fr/inserm-02409680

N. J. Watkins and M. T. Bohnsack, The box C/D and H/ACA snoRNPs: key players in the modification, processing and the dynamic folding of ribosomal RNA, Wiley Interdisciplinary Reviews: RNA, vol.3, issue.3, pp.397-414, 2011.

S. Sharma and D. L. Lafontaine, ?View From A Bridge?: A New Perspective on Eukaryotic rRNA Base Modification, Trends in Biochemical Sciences, vol.40, issue.10, pp.560-575, 2015.

Z. Shi and M. Barna, Translating the Genome in Time and Space: Specialized Ribosomes, RNA Regulons, and RNA-Binding Proteins, Annual Review of Cell and Developmental Biology, vol.31, issue.1, pp.31-54, 2015.

N. R. Genuth and M. Barna, Heterogeneity and specialized functions of translation machinery: from genes to organisms, Nature Reviews Genetics, vol.19, issue.7, pp.431-452, 2018.

K. E. Sloan, A. S. Warda, S. Sharma, K. D. Entian, D. L. Lafontaine et al., Tuning the ribosome: The influence of rRNA modification on eukaryotic ribosome biogenesis and function, RNA Biology, vol.14, issue.9, pp.1138-1152, 2016.

B. E. Maden, Identification of the locations of the methyl groups in 18 S ribosomal RNA from Xenopus laevis and man, Journal of Molecular Biology, vol.189, issue.4, pp.681-699, 1986.

B. E. Maden, Locations of methyl groups in 28 S rRNA of Xenopus laevis and man, Journal of Molecular Biology, vol.201, issue.2, pp.289-314, 1988.

H. Ma, X. Wang, J. Cai, Q. Dai, S. K. Natchiar et al., N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation, Nature Chemical Biology, vol.15, issue.1, pp.88-94, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-02409786

P. D. Hsu, D. A. Scott, J. A. Weinstein, F. A. Ran, S. Konermann et al., DNA targeting specificity of RNA-guided Cas9 nucleases, Nature Biotechnology, vol.31, issue.9, pp.827-832, 2013.

S. Sharma, J. L. Langhendries, P. Watzinger, P. Kötter, K. D. Entian et al., Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine acetyltransferases that modify tRNAs assisted by the adaptor Tan1/THUMPD1, Nucleic Acids Research, vol.43, issue.4, pp.2242-2258, 2015.

W. Kabsch, Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants, Journal of Applied Crystallography, vol.26, issue.6, pp.795-800, 1993.

P. R. Evans and G. N. Murshudov, How good are my data and what is the resolution?, Acta Crystallographica Section D Biological Crystallography, vol.69, issue.7, pp.1204-1214, 2013.

A. J. Mccoy, R. W. Grosse-kunstleve, P. D. Adams, M. D. Winn, L. C. Storoni et al., Phasercrystallographic software, Journal of Applied Crystallography, vol.40, issue.4, pp.658-674, 2007.

L. A. Kelley, S. Mezulis, C. M. Yates, M. N. Wass, and M. J. Sternberg, The Phyre2 web portal for protein modeling, prediction and analysis, Nature Protocols, vol.10, issue.6, pp.845-858, 2015.

J. Létoquart, E. Huvelle, L. Wacheul, G. Bourgeois, C. Zorbas et al., Structural and functional studies of Bud23?Trm112 reveal 18S rRNAN7-G1575 methylation occurs on late 40S precursor ribosomes, Proceedings of the National Academy of Sciences, vol.111, issue.51, pp.E5518-E5526, 2014.

P. Emsley, B. Lohkamp, W. G. Scott, and K. Cowtan, Features and development ofCoot, Acta Crystallographica Section D Biological Crystallography, vol.66, issue.4, pp.486-501, 2010.

G. Bricogne, E. Blanc, M. Brandl, C. Flensburg, P. Keller et al., , 2016.

B. Linder, A. V. Grozhik, A. O. Olarerin-george, C. Meydan, C. E. Mason et al., Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome, Nature Methods, vol.12, issue.8, pp.767-772, 2015.

J. P. Cecchini and R. Miassod, Studies on the Methylation of Cytoplasmic Ribosomal RNA from Cultured Higher Plant Cells, European Journal of Biochemistry, vol.98, issue.1, pp.203-214, 1979.

C. The-uniprot, UniProt: the universal protein knowledgebase, Nucleic Acids Research, vol.45, issue.D1, pp.D158-D169, 2016.

C. J. Sigrist, E. De-castro, L. Cerutti, B. A. Cuche, N. Hulo et al., New and continuing developments at PROSITE, Nucleic Acids Research, vol.41, issue.D1, pp.D344-D347, 2012.

V. Heurgué-hamard, S. Champ, L. Mora, T. Merkoulova-rainon, L. L. Kisselev et al., The Glutamine Residue of the Conserved GGQ Motif inSaccharomyces cerevisiaeRelease Factor eRF1 Is Methylated by the Product of theYDR140wGene, Journal of Biological Chemistry, vol.280, issue.4, pp.2439-2445, 2004.

S. Figaro, N. Scrima, R. H. Buckingham, and V. Heurgué-hamard, HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1, FEBS Letters, vol.582, issue.16, pp.2352-2356, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00348794

D. Liger, L. Mora, N. Lazar, S. Figaro, J. Henri et al., Mechanism of activation of methyltransferases involved in translation by the Trm112 ?hub? protein, Nucleic Acids Research, vol.39, issue.14, pp.6249-6259, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00624935

M. Graille, V. Heurgué-hamard, S. Champ, L. Mora, N. Scrima et al., Molecular Basis for Bacterial Class I Release Factor Methylation by PrmC, Molecular Cell, vol.20, issue.6, pp.917-927, 2005.
URL : https://hal.archives-ouvertes.fr/hal-00090289

J. M. Bujnicki, Phylogenomic analysis of 16S rRNA:(guanine?N2) methyltransferases suggests new family members and reveals highly conserved motifs and a domain structure similar to other nucleic acid amino?methyltransferases, The FASEB Journal, vol.14, issue.14, pp.2365-2368, 2000.

B. Polevoda, L. Span, and F. Sherman, The Yeast Translation Release Factors Mrf1p and Sup45p (eRF1) Are Methylated, Respectively, by the Methyltransferases Mtq1p and Mtq2p, Journal of Biological Chemistry, vol.281, issue.5, pp.2562-2571, 2005.

P. J. Thul, L. Åkesson, M. Wiking, D. Mahdessian, A. Geladaki et al., A subcellular map of the human proteome, Science, vol.356, issue.6340, p.eaal3321, 2017.

C. Franke, D. Gräfe, H. Bartsch, and M. P. Bachmann, Use of Nonradioactive Detection Method for North- and South-Western Blot, Methods in Molecular Biology, vol.1314, pp.63-71, 2015.

J. A. Kowalak, E. Bruenger, P. F. Crain, and J. A. Mccloskey, Identities and Phylogenetic Comparisons of Posttranscriptional Modifications in 16 S Ribosomal RNA fromHaloferax volcanii, Journal of Biological Chemistry, vol.275, issue.32, pp.24484-24489, 2000.

L. Domenjoud, C. Fronia, F. Uhde, and W. Engel, Sequence of human protamine 2 cDNA, Nucleic Acids Research, vol.16, issue.15, pp.7733-7733, 1988.

H. Grosjean, C. Gaspin, C. Marck, W. A. Decatur, and V. De-crécy-lagard, RNomics and Modomics in the halophilic archaea Haloferax volcanii: identification of RNA modification genes, BMC Genomics, vol.9, issue.1, p.470, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00354522

N. Leulliot, M. Chaillet, D. Durand, N. Ulryck, K. Blondeau et al., Structure of the Yeast tRNA m7G Methylation Complex, Structure, vol.16, issue.1, pp.52-61, 2008.

M. P. Guy and E. M. Phizicky, Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification, RNA Biology, vol.11, issue.12, pp.1608-1618, 2014.

P. Sledz and M. Jinek, Structural insights into the molecular mechanism of the m(6)A writer complex. eLife, vol.5, p.18434, 2016.

X. Wang, J. Feng, Y. Xue, Z. Guan, D. Zhang et al., Structural basis of N6-adenosine methylation by the METTL3?METTL14 complex, Nature, vol.534, issue.7608, pp.575-578, 2016.

G. Bourgeois, J. Létoquart, N. Van-tran, and M. Graille, Trm112, a Protein Activator of Methyltransferases Modifying Actors of the Eukaryotic Translational Apparatus, Biomolecules, vol.7, issue.4, p.7, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01948152

N. Van tran, L. Muller, R. L. Ross, R. Lestini, J. Létoquart et al., Evolutionary insights into Trm112-methyltransferase holoenzymes involved in translation between archaea and eukaryotes, Nucleic Acids Research, vol.46, issue.16, pp.8483-8499, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01910142

V. Heurgué-hamard, M. Graille, N. Scrima, N. Ulryck, S. Champ et al., The Zinc Finger Protein Ynr046w Is Plurifunctional and a Component of the eRF1 Methyltransferase in Yeast, Journal of Biological Chemistry, vol.281, issue.47, pp.36140-36148, 2006.

M. H. Mazauric, L. Dirick, S. K. Purushothaman, G. R. Björk, and B. Lapeyre, Trm112p Is a 15-kDa Zinc Finger Protein Essential for the Activity of Two tRNA and One Protein Methyltransferases in Yeast, Journal of Biological Chemistry, vol.285, issue.24, pp.18505-18515, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00509840

L. Songe-møller, E. Van-den-born, V. Leihne, C. B. Va?gbø, T. Kristoffersen et al., Mammalian ALKBH8 Possesses tRNA Methyltransferase Activity Required for the Biogenesis of Multiple Wobble Uridine Modifications Implicated in Translational Decoding, Molecular and Cellular Biology, vol.30, issue.7, pp.1814-1827, 2010.

S. Figaro, L. Wacheul, S. Schillewaert, M. Graille, E. Huvelle et al., Trm112 Is Required for Bud23-Mediated Methylation of the 18S rRNA at Position G1575, Molecular and Cellular Biology, vol.32, issue.12, pp.2254-2267, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00709211

C. Zorbas, E. Nicolas, L. Wacheul, E. Huvelle, V. Heurgué-hamard et al., The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis, Molecular Biology of the Cell, vol.26, issue.11, pp.2080-2095, 2015.

J. Létoquart, N. Van tran, V. Caroline, A. Aleksandrov, N. Lazar et al., Insights into molecular plasticity in protein complexes from Trm9-Trm112 tRNA modifying enzyme crystal structure, Nucleic Acids Research, vol.43, issue.22, pp.10989-11002, 2015.

G. Bourgeois, J. Marcoux, J. M. Saliou, S. Cianférani, and M. Graille, Activation mode of the eukaryotic m2G10tRNA methyltransferase Trm11 by its partner protein Trm112, Nucleic Acids Research, vol.45, p.gkw1271, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01953006

P. Wang, K. A. Doxtader, and Y. Nam, Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases, Molecular Cell, vol.63, issue.2, pp.306-317, 2016.

K. A. Doxtader, P. Wang, A. M. Scarborough, D. Seo, N. K. Conrad et al., Structural Basis for Regulation of METTL16, an S-Adenosylmethionine Homeostasis Factor, Molecular Cell, vol.71, issue.6, pp.1001-1011.e4, 2018.

M. Mendel, K. M. Chen, D. Homolka, P. Gos, R. R. Pandey et al., Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development, Molecular Cell, vol.71, issue.6, pp.986-1000.e11, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02976314

A. Ruszkowska, M. Ruszkowski, Z. Dauter, and J. A. Brown, Structural insights into the RNA methyltransferase domain of METTL16, Scientific Reports, vol.8, issue.1, p.5311, 2018.

S. Akichika, S. Hirano, Y. Shichino, T. Suzuki, H. Nishimasu et al., Cap-specific terminalN6-methylation of RNA by an RNA polymerase II?associated methyltransferase, Science, vol.363, issue.6423, p.eaav0080, 2018.

Y. Fu, D. Dominissini, G. Rechavi, and C. He, Gene expression regulation mediated through reversible m6A RNA methylation, Nature Reviews Genetics, vol.15, issue.5, pp.293-306, 2014.

K. D. Meyer and S. R. Jaffrey, The dynamic epitranscriptome: N6-methyladenosine and gene expression control, Nature Reviews Molecular Cell Biology, vol.15, issue.5, pp.313-326, 2014.

N. Liu and T. Pan, N6-methyladenosine?encoded epitranscriptomics, Nature Structural & Molecular Biology, vol.23, issue.2, pp.98-102, 2016.

K. E. Pendleton, B. Chen, K. Liu, O. V. Hunter, Y. Xie et al., The U6 snRNA m 6 A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention, Cell, vol.169, issue.5, pp.824-835.e14, 2017.

A. S. Warda, J. Kretschmer, P. Hackert, C. Lenz, H. Urlaub et al., Human METTL16 is a N 6 ?methyladenosine (m 6 A) methyltransferase that targets pre?mRNAs and various non?coding RNAs, EMBO reports, vol.18, issue.11, pp.2004-2014, 2017.

K. Goedecke, M. Pignot, R. S. Goody, A. J. Scheidig, and E. Weinhold, Structure of the N6-adenine DNA methyltransferase M.TaqI in complex with DNA and a cofactor analog, Nat. Struct. Biol, vol.8, pp.121-125, 2001.

M. Ameismeier, J. Cheng, O. Berninghausen, and R. Beckmann, Visualizing late states of human 40S ribosomal subunit maturation, Nature, vol.558, issue.7709, pp.249-253, 2018.

M. Safra, A. Sas-chen, R. Nir, R. Winkler, A. Nachshon et al., The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution, Nature, vol.551, issue.7679, pp.251-255, 2017.

D. Arango, D. Sturgill, N. Alhusaini, A. A. Dillman, T. J. Sweet et al., Acetylation of Cytidine in mRNA Promotes Translation Efficiency, Cell, vol.175, issue.7, pp.1872-1886.e24, 2018.

M. Ringeard, V. Marchand, E. Decroly, Y. Motorin, and Y. Bennasser, FTSJ3 is an RNA 2'-O-methyltransferase recruited by HIV to avoid innate immune sensing, Nature, vol.565, pp.500-504, 2019.
URL : https://hal.archives-ouvertes.fr/hal-01981983

V. Marchand, L. Ayadi, F. G. Ernst, J. Hertler, V. Bourguignon?igel et al., AlkAniline?Seq: Profiling of m 7 G and m 3 C RNA Modifications at Single Nucleotide Resolution, Angewandte Chemie International Edition, vol.57, issue.51, pp.16785-16790, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01928435

D. Fu, J. A. Brophy, C. T. Chan, K. A. Atmore, U. Begley et al., Human AlkB Homolog ABH8 Is a tRNA Methyltransferase Required for Wobble Uridine Modification and DNA Damage Survival, Molecular and Cellular Biology, vol.30, issue.10, pp.2449-2459, 2010.

K. Õunap, L. Leetsi, M. Matsoo, and R. Kurg, The Stability of Ribosome Biogenesis Factor WBSCR22 Is Regulated by Interaction with TRMT112 via Ubiquitin-Proteasome Pathway, PLOS ONE, vol.10, issue.7, p.e0133841, 2015.

S. Shao, J. Murray, A. Brown, J. Taunton, V. Ramakrishnan et al., Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes, Cell, vol.167, issue.5, pp.1229-1240.e15, 2016.

A. O. Olarerin-george and S. R. Jaffrey, MetaPlotR: a Perl/R pipeline for plotting metagenes of nucleotide modifications and other transcriptomic sites, Bioinformatics, vol.33, pp.1563-1564, 2017.