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A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B

The precise control of microRNA (miRNA) biosynthesis is crucial for gene regulation. Lin28A and Lin28B are selective inhibitors of biogenesis of let-7 miRNAs involved in development and tumorigenesis. Lin28A selectively inhibits let-7 biogenesis through cytoplasmic uridylation of precursor let-7 by...

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Autores principales: Suzuki, Hiroshi I, Katsura, Akihiro, Miyazono, Kohei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582986/
https://www.ncbi.nlm.nih.gov/pubmed/26080928
http://dx.doi.org/10.1111/cas.12721
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author Suzuki, Hiroshi I
Katsura, Akihiro
Miyazono, Kohei
author_facet Suzuki, Hiroshi I
Katsura, Akihiro
Miyazono, Kohei
author_sort Suzuki, Hiroshi I
collection PubMed
description The precise control of microRNA (miRNA) biosynthesis is crucial for gene regulation. Lin28A and Lin28B are selective inhibitors of biogenesis of let-7 miRNAs involved in development and tumorigenesis. Lin28A selectively inhibits let-7 biogenesis through cytoplasmic uridylation of precursor let-7 by TUT4 terminal uridyl transferase and subsequent degradation by Dis3l2 exonuclease. However, a role of this uridylation pathway remains unclear in let-7 blockade by Lin28B, a paralog of Lin28A, while Lin28B is reported to engage a distinct mechanism in the nucleus to suppress let-7. Here we revisit a functional link between Lin28B and the uridylation pathway with a focus on let-7 metabolism in cancer cells. Both Lin28A and Lin28B interacted with Dis3l2 in the cytoplasm, and silencing of Dis3l2 upregulated uridylated pre-let-7 in both Lin28A- and Lin28B-expressing cancer cell lines. In addition, we found that amounts of let-7 precursors influenced intracellular localization of Lin28B. Furthermore, we found that MCPIP1 (Zc3h12a) ribonuclease was also involved in degradation of both non-uridylated and uridylated pre-let-7. Cancer transcriptome analysis showed association of expression levels of Lin28B and uridylation pathway components, TUT4 and Dis3l2, in various human cancer cells and hepatocellular carcinoma. Collectively, these results suggest that cytoplasmic uridylation pathway actively participates in blockade of let-7 biogenesis by Lin28B.
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spelling pubmed-45829862015-10-05 A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B Suzuki, Hiroshi I Katsura, Akihiro Miyazono, Kohei Cancer Sci Original Articles The precise control of microRNA (miRNA) biosynthesis is crucial for gene regulation. Lin28A and Lin28B are selective inhibitors of biogenesis of let-7 miRNAs involved in development and tumorigenesis. Lin28A selectively inhibits let-7 biogenesis through cytoplasmic uridylation of precursor let-7 by TUT4 terminal uridyl transferase and subsequent degradation by Dis3l2 exonuclease. However, a role of this uridylation pathway remains unclear in let-7 blockade by Lin28B, a paralog of Lin28A, while Lin28B is reported to engage a distinct mechanism in the nucleus to suppress let-7. Here we revisit a functional link between Lin28B and the uridylation pathway with a focus on let-7 metabolism in cancer cells. Both Lin28A and Lin28B interacted with Dis3l2 in the cytoplasm, and silencing of Dis3l2 upregulated uridylated pre-let-7 in both Lin28A- and Lin28B-expressing cancer cell lines. In addition, we found that amounts of let-7 precursors influenced intracellular localization of Lin28B. Furthermore, we found that MCPIP1 (Zc3h12a) ribonuclease was also involved in degradation of both non-uridylated and uridylated pre-let-7. Cancer transcriptome analysis showed association of expression levels of Lin28B and uridylation pathway components, TUT4 and Dis3l2, in various human cancer cells and hepatocellular carcinoma. Collectively, these results suggest that cytoplasmic uridylation pathway actively participates in blockade of let-7 biogenesis by Lin28B. John Wiley & Sons, Ltd 2015-09 2015-07-14 /pmc/articles/PMC4582986/ /pubmed/26080928 http://dx.doi.org/10.1111/cas.12721 Text en © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Suzuki, Hiroshi I
Katsura, Akihiro
Miyazono, Kohei
A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B
title A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B
title_full A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B
title_fullStr A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B
title_full_unstemmed A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B
title_short A role of uridylation pathway for blockade of let-7 microRNA biogenesis by Lin28B
title_sort role of uridylation pathway for blockade of let-7 microrna biogenesis by lin28b
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582986/
https://www.ncbi.nlm.nih.gov/pubmed/26080928
http://dx.doi.org/10.1111/cas.12721
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