8GU3

Crystal structure of Caenorhabditis elegans METT-10 methyltransferase domain

Summary for 8GU3

• Entry DOI: 10.2210/pdb8gu3/pdb
• Descriptor: U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase (1 entity in total)
• Functional Keywords: sam homeostasis, u6 snrna, transferase
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 1
• Total formula weight: 36504.77

Authors

Ju, J.,Tomita, K. (deposition date: 2022-09-09, release date: 2023-02-01, Last modification date: 2023-11-29)

Primary citation

Ju, J.,Aoyama, T.,Yashiro, Y.,Yamashita, S.,Kuroyanagi, H.,Tomita, K.
Structure of the Caenorhabditis elegans m6A methyltransferase METT10 that regulates SAM homeostasis.
Nucleic Acids Res., 51:2434-2446, 2023

PubMed Abstract: In Caenorhabditis elegans, the N6-methyladenosine (m6A) modification by METT10, at the 3'-splice sites in S-adenosyl-l-methionine (SAM) synthetase (sams) precursor mRNA (pre-mRNA), inhibits sams pre-mRNA splicing, promotes alternative splicing coupled with nonsense-mediated decay of the pre-mRNAs, and thereby maintains the cellular SAM level. Here, we present structural and functional analyses of C. elegans METT10. The structure of the N-terminal methyltransferase domain of METT10 is homologous to that of human METTL16, which installs the m6A modification in the 3'-UTR hairpins of methionine adenosyltransferase (MAT2A) pre-mRNA and regulates the MAT2A pre-mRNA splicing/stability and SAM homeostasis. Our biochemical analysis suggested that C. elegans METT10 recognizes the specific structural features of RNA surrounding the 3'-splice sites of sams pre-mRNAs, and shares a similar substrate RNA recognition mechanism with human METTL16. C. elegans METT10 also possesses a previously unrecognized functional C-terminal RNA-binding domain, kinase associated 1 (KA-1), which corresponds to the vertebrate-conserved region (VCR) of human METTL16. As in human METTL16, the KA-1 domain of C. elegans METT10 facilitates the m6A modification of the 3'-splice sites of sams pre-mRNAs. These results suggest the well-conserved mechanisms for the m6A modification of substrate RNAs between Homo sapiens and C. elegans, despite their different regulation mechanisms for SAM homeostasis.

PubMed: 36794723
DOI: 10.1093/nar/gkad081

Experimental method

X-RAY DIFFRACTION (3.01 Å)