The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans
Open accessAbstract
The let-7 microRNA (miRNA) is an ultraconserved regulator of stem cell differentiation and developmental timing and a candidate tumor suppressor. Here we show that LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 processing in Caenorhabditis elegans. We demonstrate that lin-28 is necessary and sufficient to block let-7 activity in vivo; LIN-28 directly binds let-7 pre-miRNA to prevent Dicer processing. Moreover, we have identified a poly(U) polymerase, PUP-2, which regulates the stability of LIN-28–blockaded let-7 pre-miRNA and contributes to LIN-28–dependent regulation of let-7 during development. We show that PUP-2 and LIN-28 interact directly, and that LIN-28 stimulates uridylation of let-7 pre-miRNA by PUP-2 in vitro. Our results demonstrate that LIN-28 and let-7 form an ancient regulatory switch, conserved from nematodes to humans, and provide insight into the mechanism of LIN-28 action in vivo. Uridylation by a PUP-2 ortholog might regulate let-7 and additional miRNAs in other species. Given the roles of Lin28 and let-7 in stem cell and cancer biology, we propose that such poly(U) polymerases are potential therapeutic targets.
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Cites
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The widespread regulation of microRNA biogenesis, function and decay
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Posttranscriptional Regulation of MicroRNA Biogenesis in Animals
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Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
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Lin28: Primal Regulator of Growth and Metabolism in Stem Cells
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Self-citation
Metadata
- Authors
- Lehrbach, N. J., Armisen, J., Lightfoot, H. L., Murfitt, K. J., Bugaut, A., Balasubramanian, S., & Miska, E. A.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2009-08-27
- Volume
- 16
- Issue
- 10
- Pages
- 1016-1020
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2105698711
- Cited by
- 229
- References
- 7
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- green
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- Lehrbach, N. J., Armisen, J., Lightfoot, H. L., Murfitt, K. J., Bugaut, A., Balasubramanian, S., & Miska, E. A. (2009). LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.1675
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