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TitleCryo-EM structure of human TUT1:U6 snRNA complex.
Journal, issue, pagesNucleic Acids Res, Vol. 53, Issue 2, Year 2025
Publish dateJan 11, 2025
AuthorsSeisuke Yamashita / Kozo Tomita /
PubMed AbstractU6 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 ...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.
External linksNucleic Acids Res / PubMed:39831302 / PubMed Central
MethodsEM (single particle)
Resolution3.21 - 3.83 Å
Structure data

EMDB-61234: Cryo-EM structure of human TUT1 complexed with U6 snRNA (consensus map)
Method: EM (single particle) / Resolution: 3.21 Å

EMDB-61235: Cryo-EM structure of human TUT1 complexed with U6 snRNA (KA-1 focused map)
Method: EM (single particle) / Resolution: 3.83 Å

EMDB-61236: Cryo-EM structure of human TUT1 complexed with U6 snRNA (5'-RNA focused map)
Method: EM (single particle) / Resolution: 3.72 Å

61237

9j8p

EMDB-61237, PDB-9j8p:
Cryo-EM structure of human TUT1 complexed with U6 snRNA
Method: EM (single particle) / Resolution: 3.21 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsTRANSFERASE / Complex / TUTase

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