Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA

Inha Heo; Chirlmin Joo; Jun Cho; Minju Ha; Jinju Han; V. Narry Kim

doi:10.1016/j.molcel.2008.09.014

Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA

Inha Heo, Chirlmin Joo, Jun Cho, Minju Ha, Jinju Han, V. Narry Kim

Department of Physics

Research output: Contribution to journal › Article › peer-review

649 Scopus citations

Abstract

The precise control of microRNA (miRNA) biogenesis is critical for embryonic development and normal cellular functions, and its dysregulation is often associated with human diseases. Though the birth and maturation pathway of miRNA has been established, the regulation and death pathway remains largely unknown. Here, we report the RNA-binding proteins, Lin28a and Lin28b, as posttranscriptional repressors of let-7 miRNA biogenesis. We observe that the Lin28 proteins act mainly in the cytoplasm by inducing uridylation of precursor let-7 (pre-let-7) at its 3′ end. The uridylated pre-let-7 (up-let-7) fails Dicer processing and undergoes degradation. We provide a mechanism for the posttranscriptional regulation of miRNA biogenesis by Lin28 which is highly expressed in undifferentiated cells and certain cancer cells. The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis.

Original language	English
Pages (from-to)	276-284
Number of pages	9
Journal	Molecular Cell
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2008.09.014
State	Published - 24 Oct 2008

Keywords

PROTEINS
RNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.molcel.2008.09.014

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title = "Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA",

abstract = "The precise control of microRNA (miRNA) biogenesis is critical for embryonic development and normal cellular functions, and its dysregulation is often associated with human diseases. Though the birth and maturation pathway of miRNA has been established, the regulation and death pathway remains largely unknown. Here, we report the RNA-binding proteins, Lin28a and Lin28b, as posttranscriptional repressors of let-7 miRNA biogenesis. We observe that the Lin28 proteins act mainly in the cytoplasm by inducing uridylation of precursor let-7 (pre-let-7) at its 3′ end. The uridylated pre-let-7 (up-let-7) fails Dicer processing and undergoes degradation. We provide a mechanism for the posttranscriptional regulation of miRNA biogenesis by Lin28 which is highly expressed in undifferentiated cells and certain cancer cells. The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis.",

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author = "Inha Heo and Chirlmin Joo and Jun Cho and Minju Ha and Jinju Han and Kim, {V. Narry}",

note = "Funding Information: We are grateful to the members of our laboratory for their helpful discussion and critical reading of the manuscript. We also thank Kyung Hoon Kim and Dr. Se Won Seo for their advice on protein purification and Drs. Guhung Jung and Seung Hwan Hong for the gift of cell lines. This work was supported by the Creative Research Initiatives Program (R16-2007-073-01000-0) and the BK21 Research Fellowships (I.H., C.J., M.H., and J.H.) from the Ministry of Education, Science and Technology of Korea. ",

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AU - Kim, V. Narry

N1 - Funding Information: We are grateful to the members of our laboratory for their helpful discussion and critical reading of the manuscript. We also thank Kyung Hoon Kim and Dr. Se Won Seo for their advice on protein purification and Drs. Guhung Jung and Seung Hwan Hong for the gift of cell lines. This work was supported by the Creative Research Initiatives Program (R16-2007-073-01000-0) and the BK21 Research Fellowships (I.H., C.J., M.H., and J.H.) from the Ministry of Education, Science and Technology of Korea.

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N2 - The precise control of microRNA (miRNA) biogenesis is critical for embryonic development and normal cellular functions, and its dysregulation is often associated with human diseases. Though the birth and maturation pathway of miRNA has been established, the regulation and death pathway remains largely unknown. Here, we report the RNA-binding proteins, Lin28a and Lin28b, as posttranscriptional repressors of let-7 miRNA biogenesis. We observe that the Lin28 proteins act mainly in the cytoplasm by inducing uridylation of precursor let-7 (pre-let-7) at its 3′ end. The uridylated pre-let-7 (up-let-7) fails Dicer processing and undergoes degradation. We provide a mechanism for the posttranscriptional regulation of miRNA biogenesis by Lin28 which is highly expressed in undifferentiated cells and certain cancer cells. The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis.

AB - The precise control of microRNA (miRNA) biogenesis is critical for embryonic development and normal cellular functions, and its dysregulation is often associated with human diseases. Though the birth and maturation pathway of miRNA has been established, the regulation and death pathway remains largely unknown. Here, we report the RNA-binding proteins, Lin28a and Lin28b, as posttranscriptional repressors of let-7 miRNA biogenesis. We observe that the Lin28 proteins act mainly in the cytoplasm by inducing uridylation of precursor let-7 (pre-let-7) at its 3′ end. The uridylated pre-let-7 (up-let-7) fails Dicer processing and undergoes degradation. We provide a mechanism for the posttranscriptional regulation of miRNA biogenesis by Lin28 which is highly expressed in undifferentiated cells and certain cancer cells. The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis.

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Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA

Abstract

Keywords

UN SDGs

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