9J8P

Cryo-EM structure of human TUT1 complexed with U6 snRNA

Summary for 9J8P

• Entry DOI: 10.2210/pdb9j8p/pdb
• EMDB information: 61237
• Descriptor: Speckle targeted PIP5K1A-regulated poly(A) polymerase, U6 snRNA, ZINC ION (3 entities in total)
• Functional Keywords: complex, tutase, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 129189.81

Authors

Yamashita, S.,Tomita, K. (deposition date: 2024-08-21, release date: 2025-01-01, Last modification date: 2025-02-05)

Primary citation

Yamashita, S.,Tomita, K.
Cryo-EM structure of human TUT1:U6 snRNA complex.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: U6 snRNA (small nuclear ribonucleic acid) is a ribozyme that catalyzes pre-messenger RNA (pre-mRNA) splicing and undergoes epitranscriptomic modifications. After transcription, the 3'-end of U6 snRNA is oligo-uridylylated by the multi-domain terminal uridylyltransferase (TUTase), TUT1. The 3'- oligo-uridylylated tail of U6 snRNA is crucial for U4/U6 di-snRNP (small nuclear ribonucleoprotein) formation and pre-mRNA splicing. Here, we present the cryo-electron microscopy structure of the human TUT1:U6 snRNA complex. The AUA-rich motif between the 5'-short stem-loop and the telestem of U6 snRNA is clamped by the N-terminal zinc finger (ZF)-RNA recognition motif and the catalytic Palm of TUT1, and the telestem is gripped by the N-terminal ZF and the Fingers, positioning the 3'-end of the telestem in the catalytic pocket. The internal stem-loop in the 3'-stem-loop of U6 snRNA is anchored by the C-terminal kinase-associated 1 domain, preventing U6 snRNA from dislodging on the TUT1 surface during oligo-uridylylation. TUT1 recognizes the sequence and structural features of U6 snRNA, and holds the entire U6 snRNA body using multiple domains to ensure oligo-uridylylation. This highlights the specificity of TUT1 as a U6 snRNA-targeting TUTase.

PubMed: 39831302
DOI: 10.1093/nar/gkae1314

Experimental method

ELECTRON MICROSCOPY (3.21 Å)