9M86

Crystal structure of SpMETTL16 kinase associated 1 domain in complex with U6 snRNA internal stem loop

Summary for 9M86

• Entry DOI: 10.2210/pdb9m86/pdb
• Descriptor: U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase, RNA (31-MER) (2 entities in total)
• Functional Keywords: m6a methyltransferase, u6 snrna, protein-rna complex, splicing, transferase, transferase-rna complex, transferase/rna
• Biological source: Schizosaccharomyces pombe (fission yeast); More
• Total number of polymer chains: 4
• Total formula weight: 50139.92

Authors

Ju, J.,Tomita, K. (deposition date: 2025-03-11, release date: 2025-08-06, Last modification date: 2025-09-24)

Primary citation

Ju, J.,Tomita, K.
Structures and mechanisms of U6 snRNA m 6 A modification by METTL16.
Nat Commun, 16:7708-7708, 2025

PubMed Abstract: The N-methyladenosine (mA) 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 mA 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 mA. 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 mA 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.

PubMed: 40841561
DOI: 10.1038/s41467-025-63021-0

Experimental method

X-RAY DIFFRACTION (2.795 Å)