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The human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27.
Nucleic Acids Res. 2020 Jul 01 [Online ahead of print]NA

Abstract

MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression and their dysfunction is often associated with cancer. Alongside the canonical miRNA biogenesis pathway involving stepwise processing and export of pri- and pre-miRNA transcripts by the microprocessor complex, Exportin 5 and Dicer, several alternative mechanisms of miRNA production have been described. Here, we reveal that the atypical box C/D snoRNA U3, which functions as a scaffold during early ribosome assembly, is a miRNA source. We show that a unique stem-loop structure in the 5' domain of U3 is processed to form short RNA fragments that associate with Argonaute. miR-U3 production is independent of Drosha, and an increased amount of U3 in the cytoplasm in the absence of Dicer suggests that a portion of the full length snoRNA is exported to the cytoplasm where it is efficiently processed into miRNAs. Using reporter assays, we demonstrate that miR-U3 can act as a low proficiency miRNA in vivo and our data support the 3' UTR of the sortin nexin SNX27 mRNA as an endogenous U3-derived miRNA target. We further reveal that perturbation of U3 snoRNP assembly induces miR-U3 production, highlighting potential cross-regulation of target mRNA expression and ribosome production.

Authors+Show Affiliations

Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. Junior Research Group Medical RNA Biology, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany.Junior Research Group Medical RNA Biology, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany.Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.Junior Research Group Medical RNA Biology, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany.Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. Göttingen Center for Molecular Biosciences, Georg-August University, Göttingen, Justus-von-Liebig-Weg 11, 37077 Germany. Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32609813

Citation

Lemus-Diaz, Nicolas, et al. "The Human Box C/D snoRNA U3 Is a miRNA Source and miR-U3 Regulates Expression of Sortin Nexin 27." Nucleic Acids Research, 2020.
Lemus-Diaz N, Ferreira RR, Bohnsack KE, et al. The human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27. Nucleic Acids Res. 2020.
Lemus-Diaz, N., Ferreira, R. R., Bohnsack, K. E., Gruber, J., & Bohnsack, M. T. (2020). The human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa549
Lemus-Diaz N, et al. The Human Box C/D snoRNA U3 Is a miRNA Source and miR-U3 Regulates Expression of Sortin Nexin 27. Nucleic Acids Res. 2020 Jul 1; PubMed PMID: 32609813.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27. AU - Lemus-Diaz,Nicolas, AU - Ferreira,Rafael Rinaldi, AU - Bohnsack,Katherine E, AU - Gruber,Jens, AU - Bohnsack,Markus T, Y1 - 2020/07/01/ PY - 2020/06/22/accepted PY - 2020/05/29/revised PY - 2019/10/25/received PY - 2020/7/2/entrez PY - 2020/7/2/pubmed PY - 2020/7/2/medline JF - Nucleic acids research JO - Nucleic Acids Res. N2 - MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression and their dysfunction is often associated with cancer. Alongside the canonical miRNA biogenesis pathway involving stepwise processing and export of pri- and pre-miRNA transcripts by the microprocessor complex, Exportin 5 and Dicer, several alternative mechanisms of miRNA production have been described. Here, we reveal that the atypical box C/D snoRNA U3, which functions as a scaffold during early ribosome assembly, is a miRNA source. We show that a unique stem-loop structure in the 5' domain of U3 is processed to form short RNA fragments that associate with Argonaute. miR-U3 production is independent of Drosha, and an increased amount of U3 in the cytoplasm in the absence of Dicer suggests that a portion of the full length snoRNA is exported to the cytoplasm where it is efficiently processed into miRNAs. Using reporter assays, we demonstrate that miR-U3 can act as a low proficiency miRNA in vivo and our data support the 3' UTR of the sortin nexin SNX27 mRNA as an endogenous U3-derived miRNA target. We further reveal that perturbation of U3 snoRNP assembly induces miR-U3 production, highlighting potential cross-regulation of target mRNA expression and ribosome production. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/32609813/The_human_box_C/D_snoRNA_U3_is_a_miRNA_source_and_miR-U3_regulates_expression_of_sortin_nexin_27 L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkaa549 DB - PRIME DP - Unbound Medicine ER -
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