8OST

Structure of human terminal uridylyltransferase 4 (TUT4, ZCCHC11) in complex with pre-let7g miRNA and Lin28A

Summary for 8OST

• Entry DOI: 10.2210/pdb8ost/pdb
• EMDB information: 17164
• Descriptor: Terminal uridylyltransferase 4, Protein lin-28 homolog A, pre-let7-g, ... (4 entities in total)
• Functional Keywords: polymerase, uridylation, rna maturation and turnover control, rna, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 230630.76

Authors

Gilbert, R.J.,Yi, G.,Ye, M. (deposition date: 2023-04-20, release date: 2024-07-17, Last modification date: 2024-09-25)

Primary citation

Yi, G.,Ye, M.,Carrique, L.,El-Sagheer, A.,Brown, T.,Norbury, C.J.,Zhang, P.,Gilbert, R.J.C.
Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs.
Nat.Struct.Mol.Biol., 31:1426-1438, 2024

PubMed Abstract: Tumor-suppressor let-7 pre-microRNAs (miRNAs) are regulated by terminal uridylyltransferases TUT7 and TUT4 that either promote let-7 maturation by adding a single uridine nucleotide to the pre-miRNA 3' end or mark them for degradation by the addition of multiple uridines. Oligo-uridylation is increased in cells by enhanced TUT7/4 expression and especially by the RNA-binding pluripotency factor LIN28A. Using cryogenic electron microscopy, we captured high-resolution structures of active forms of TUT7 alone, of TUT7 plus pre-miRNA and of both TUT7 and TUT4 bound with pre-miRNA and LIN28A. Our structures reveal that pre-miRNAs engage the enzymes in fundamentally different ways depending on the presence of LIN28A, which clamps them onto the TUTs to enable processive 3' oligo-uridylation. This study reveals the molecular basis for mono- versus oligo-uridylation by TUT7/4, as determined by the presence of LIN28A, and thus their mechanism of action in the regulation of cell fate and in cancer.

PubMed: 39054354
DOI: 10.1038/s41594-024-01357-9

Experimental method

ELECTRON MICROSCOPY (3.69 Å)