2025-08-21 東京大学
METTL16・SAM・U6 snRNA三者複合体構造
<関連情報>
- https://www.k.u-tokyo.ac.jp/information/category/press/11713.html
- https://www.k.u-tokyo.ac.jp/information/upload/f196f5e470a06239429ae98183f23acad9d2072e.pdf
- https://www.nature.com/articles/s41467-025-63021-0
METTL16によるU6 snRNAのm6A修飾の構造とメカニズム Structures and mechanisms of U6 snRNA m6A modification by METTL16
Jue Ju & Kozo Tomita
Nature Communications Published:21 August 2025
DOI:https://doi.org/10.1038/s41467-025-63021-0
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.
