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Cited by 229

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LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans

Open access
Lehrbach, Nicolas J, Armisen, Javier, Lightfoot, Helen L, Murfitt, Kenneth J, Bugaut, Anthony, Balasubramanian, Shankar, Miska, Eric A·2009·Nature Structural & Molecular Biology

Abstract

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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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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CoChat. (2026). Citation check: LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans. https://app.cochat.ai/papers/10.1038/nsmb.1675
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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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