LIN28 Selectively Modulates a Subclass of Let-7 MicroRNAs

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1 LIN 28 selectively modulates a subclass of let - 7 microRNAs

Dmytro Ustianenko, Hua-Sheng Chiu, Sebastien M. Weyn-Vanhentenryck, Pavel Sumazin, Chaolin Zhang Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA Texas Children’s Cancer Center, Department of Pediatrics, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston...

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Molecular Basis for Interaction of let-7 MicroRNAs with Lin28

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression. Among these, members of the let-7 miRNA family control many cell-fate determination genes to influence pluripotency, differentiation, and transformation. Lin28 is a specific, posttranscriptional inhibitor of let-7 biogenesis. We report crystal structures of mouse Lin28 in complex with sequences from let-7d, let-...

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Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds ...

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The Lin28 cold-shock domain remodels pre-let-7 microRNA

The RNA-binding protein Lin28 regulates the processing of a developmentally important group of microRNAs, the let-7 family. Lin28 blocks the biogenesis of let-7 in embryonic stem cells and thereby prevents differentiation. It was shown that both RNA-binding domains (RBDs) of this protein, the cold-shock domain (CSD) and the zinc-knuckle domain (ZKD) are indispensable for pri- or pre-let-7 bindi...

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ژورنال

عنوان ژورنال: Molecular Cell

سال: 2018

ISSN: 1097-2765

DOI: 10.1016/j.molcel.2018.06.029