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The 18S ribosomal RNA m 6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila
Author(s) -
Leismann Jessica,
Spagnuolo Mariangela,
Pradhan Mihika,
Wacheul Ludivine,
Vu Minh Anh,
Musheev Michael,
Mier Pablo,
AndradeNavarro Miguel A,
Graille Marc,
Niehrs Christof,
Lafontaine Denis LJ,
Roignant JeanYves
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949443
Subject(s) - biology , ribosomal rna , rna , ribosome , genetics , 18s ribosomal rna , methyltransferase , 5.8s ribosomal rna , non coding rna , ribosome biogenesis , small nucleolar rna , gene , microbiology and biotechnology , methylation
RNA modifications have recently emerged as an important layer of gene regulation. N6‐methyladenosine (m 6 A) is the most prominent modification on eukaryotic messenger RNA and has also been found on noncoding RNA , including ribosomal and small nuclear RNA . Recently, several m 6 A methyltransferases were identified, uncovering the specificity of m 6 A deposition by structurally distinct enzymes. In order to discover additional m 6 A enzymes, we performed an RNA i screen to deplete annotated orthologs of human methyltransferase‐like proteins ( METTL s) in Drosophila cells and identified CG 9666, the ortholog of human METTL 5. We show that CG 9666 is required for specific deposition of m 6 A on 18S ribosomal RNA via direct interaction with the Drosophila ortholog of human TRMT 112, CG 12975. Depletion of CG 9666 yields a subsequent loss of the 18S rRNA m 6 A modification, which lies in the vicinity of the ribosome decoding center; however, this does not compromise rRNA maturation. Instead, a loss of CG 9666‐mediated m 6 A impacts fly behavior, providing an underlying molecular mechanism for the reported human phenotype in intellectual disability. Thus, our work expands the repertoire of m 6 A methyltransferases, demonstrates the specialization of these enzymes, and further addresses the significance of ribosomal RNA modifications in gene expression and animal behavior.