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Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
by
Gregory, Richard I
, Hagan, John P
, Piskounova, Elena
in
Animals
/ Binding sites
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Cancer
/ Catalysis
/ Cell Line, Tumor
/ DNA binding proteins
/ DNA-Binding Proteins - metabolism
/ Embryonic stem cells
/ Embryonic Stem Cells - metabolism
/ Genes, Reporter
/ Genetic aspects
/ Life Sciences
/ Membrane Biology
/ Mice
/ MicroRNAs - metabolism
/ Models, Genetic
/ Molecular biology
/ Oocytes - metabolism
/ Physiological aspects
/ Protein Structure
/ Protein Structure, Tertiary
/ Reverse Transcriptase Polymerase Chain Reaction
/ Ribonucleic acid
/ RNA
/ RNA, Messenger - metabolism
/ RNA-Binding Proteins - metabolism
/ RNA-Binding Proteins - physiology
/ Rodents
/ Stem cells
/ Zinc Fingers
2009
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Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
by
Gregory, Richard I
, Hagan, John P
, Piskounova, Elena
in
Animals
/ Binding sites
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Cancer
/ Catalysis
/ Cell Line, Tumor
/ DNA binding proteins
/ DNA-Binding Proteins - metabolism
/ Embryonic stem cells
/ Embryonic Stem Cells - metabolism
/ Genes, Reporter
/ Genetic aspects
/ Life Sciences
/ Membrane Biology
/ Mice
/ MicroRNAs - metabolism
/ Models, Genetic
/ Molecular biology
/ Oocytes - metabolism
/ Physiological aspects
/ Protein Structure
/ Protein Structure, Tertiary
/ Reverse Transcriptase Polymerase Chain Reaction
/ Ribonucleic acid
/ RNA
/ RNA, Messenger - metabolism
/ RNA-Binding Proteins - metabolism
/ RNA-Binding Proteins - physiology
/ Rodents
/ Stem cells
/ Zinc Fingers
2009
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Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
by
Gregory, Richard I
, Hagan, John P
, Piskounova, Elena
in
Animals
/ Binding sites
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Cancer
/ Catalysis
/ Cell Line, Tumor
/ DNA binding proteins
/ DNA-Binding Proteins - metabolism
/ Embryonic stem cells
/ Embryonic Stem Cells - metabolism
/ Genes, Reporter
/ Genetic aspects
/ Life Sciences
/ Membrane Biology
/ Mice
/ MicroRNAs - metabolism
/ Models, Genetic
/ Molecular biology
/ Oocytes - metabolism
/ Physiological aspects
/ Protein Structure
/ Protein Structure, Tertiary
/ Reverse Transcriptase Polymerase Chain Reaction
/ Ribonucleic acid
/ RNA
/ RNA, Messenger - metabolism
/ RNA-Binding Proteins - metabolism
/ RNA-Binding Proteins - physiology
/ Rodents
/ Stem cells
/ Zinc Fingers
2009
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Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
Journal Article
Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
2009
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Overview
The let-7 microRNA has been implicated in development and disease. Its expression must thus be tightly regulated, and previously uridylation and Lin28 were implicated in let-7 stability. Zcchc11 is now shown to be the uridylase that mediates pre–let-7 modification and regulates mature let-7 levels and activity in mouse embryonic stem cells.
Lin28 and Lin28B, two developmentally regulated RNA-binding proteins and likely proto-oncogenes, selectively inhibit the maturation of let-7 family microRNAs (miRNAs) in embryonic stem cells and certain cancer cell lines. Moreover, let-7 precursors (pre–let-7) were previously found to be terminally uridylated in a Lin28-dependent fashion. Here we identify Zcchc11 (zinc finger, CCHC domain containing 11) as the 3′ terminal uridylyl transferase (TUTase) responsible for Lin28-mediated pre–let-7 uridylation and subsequent blockade of let-7 processing in mouse embryonic stem cells. We demonstrate that Zcchc11 activity is UTP-dependent, selective for let-7 and recruited by Lin28. Furthermore, knockdown of either Zcchc11 or Lin28, or overexpression of a catalytically inactive TUTase, relieves the selective inhibition of let-7 processing and leads to the accumulation of mature let-7 miRNAs and repression of let-7 target reporter genes. Our results establish a role for Zcchc11-catalyzed pre–let-7 uridylation in the control of miRNA biogenesis.
Publisher
Nature Publishing Group US,Nature Publishing Group
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