{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ju J"],"funding":["MEXT | Japan Society for the Promotion of Science","MEXT | Japan Society for the Promotion of Science (JSPS)","Japan Agency for Medical Research and Development","Japan Agency for Medical Research and Development (AMED)"],"pagination":["7708"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371086"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["The N6-methyladenosine (m6A) modification in U6 snRNA, catalyzed by METTL16 using S-adenosylmethionine (SAM) as the methyl donor, is required for efficient and accurate pre-mRNA splicing. However, the mechanism by which METTL16 modifies U6 snRNA with m6A remains elusive. Here, we present cryo-EM structures of METTL16 in complex with U6 snRNA, providing insights into the METTL16-mediated modification of U6 snRNA with m6A. The structures reveal that U6 snRNA is recruited to METTL16 through specific interactions between the C-terminal kinase-associated 1 (KA-1) domain of METTL16 and the internal stem-loop (ISL) of U6 snRNA. Upon SAM binding to the catalytic pocket within the N-terminal methyltransferase domain (MTD), U6 snRNA undergoes a structural rearrangement that positions the target adenine-containing motif at the catalytic site. This conformational change is followed by an additional structural adjustment of U6 snRNA into a productive conformation, bringing the target adenosine closer to SAM within the catalytic pocket and thereby ensuring efficient m6A modification. The KA-1 domain functions as a scaffold for initial substrate recognition and facilitates the subsequent dynamic methylation process within the MTD, highlighting the cooperative roles of METTL16 domains for U6 snRNA modification."],"journal":["Nature communications"],"pubmed_title":["Structures and mechanisms of U6 snRNA m<sup>6</sup>A modification by METTL16."],"pmcid":["PMC12371086"],"funding_grant_id":["26113002","18H03980","23H00368","JP23ama121002"],"pubmed_authors":["Ju J","Tomita K"],"additional_accession":[]},"is_claimable":false,"name":"Structures and mechanisms of U6 snRNA m<sup>6</sup>A modification by METTL16.","description":"The N6-methyladenosine (m6A) modification in U6 snRNA, catalyzed by METTL16 using S-adenosylmethionine (SAM) as the methyl donor, is required for efficient and accurate pre-mRNA splicing. However, the mechanism by which METTL16 modifies U6 snRNA with m6A remains elusive. Here, we present cryo-EM structures of METTL16 in complex with U6 snRNA, providing insights into the METTL16-mediated modification of U6 snRNA with m6A. The structures reveal that U6 snRNA is recruited to METTL16 through specific interactions between the C-terminal kinase-associated 1 (KA-1) domain of METTL16 and the internal stem-loop (ISL) of U6 snRNA. Upon SAM binding to the catalytic pocket within the N-terminal methyltransferase domain (MTD), U6 snRNA undergoes a structural rearrangement that positions the target adenine-containing motif at the catalytic site. This conformational change is followed by an additional structural adjustment of U6 snRNA into a productive conformation, bringing the target adenosine closer to SAM within the catalytic pocket and thereby ensuring efficient m6A modification. The KA-1 domain functions as a scaffold for initial substrate recognition and facilitates the subsequent dynamic methylation process within the MTD, highlighting the cooperative roles of METTL16 domains for U6 snRNA modification.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-08T06:54:09.166Z","creation":"2026-04-07T23:31:37.856Z"},"accession":"S-EPMC12371086","cross_references":{"pubmed":["40841561"],"doi":["10.1038/s41467-025-63021-0"]}}