Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs
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 increa...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2024
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| _version_ | 1826314544846209024 |
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| author | Yi, G Ye, M Carrique, L El-Sagheer, A Brown, T Norbury, CJ Zhang, P Gilbert, RJC |
| author_facet | Yi, G Ye, M Carrique, L El-Sagheer, A Brown, T Norbury, CJ Zhang, P Gilbert, RJC |
| author_sort | Yi, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:35:40Z |
| format | Journal article |
| id | oxford-uuid:d34b6f3e-93bf-49c8-a752-a376db8d66ee |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:35:40Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:d34b6f3e-93bf-49c8-a752-a376db8d66ee2024-09-16T20:10:06ZStructural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d34b6f3e-93bf-49c8-a752-a376db8d66eeEnglishJisc Publications RouterNature Research2024Yi, GYe, MCarrique, LEl-Sagheer, ABrown, TNorbury, CJZhang, PGilbert, RJCTumor-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. |
| spellingShingle | Yi, G Ye, M Carrique, L El-Sagheer, A Brown, T Norbury, CJ Zhang, P Gilbert, RJC Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs |
| title | Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs |
| title_full | Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs |
| title_fullStr | Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs |
| title_full_unstemmed | Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs |
| title_short | Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs |
| title_sort | structural basis for activity switching in polymerases determining the fate of let 7 pre mirnas |
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