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

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Item Type:Article
Title:The Lin28 cold-shock domain remodels pre-let-7 microRNA
Creators Name:Mayr, F. and Schütz, A. and Dge, N. and Heinemann, U.
Abstract: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 binding and blocking its maturation. Here, we systematically examined the nucleic acid-binding preferences of the Lin28 RBDs and determined the crystal structure of the Lin28 CSD in the absence and presence of nucleic acids. Both RNA-binding domains bind to single-stranded nucleic acids with the ZKD mediating specific binding to a conserved GGAG motif and the CSD showing only limited sequence specificity. However, only the isolated Lin28 CSD, but not the ZKD, can bind with a reasonable affinity to pre-let-7 and thus is able to remodel the terminal loop of pre-let-7 including the Dicer cleavage site. Further mutagenesis studies reveal that the Lin28 CSD induces a conformational change in the terminal loop of pre-let-7 and thereby facilitates a subsequent specific binding of the Lin28 ZKD to the conserved GGAG motif.
Keywords:Binding Sites, DNA-Binding Proteins, MicroRNAs, Molecular Models, Nucleic Acid Conformation, Nucleotides, Post-Transcriptional RNA Processing, Protein Binding, RNA, RNA-Binding Proteins, RNA Precursors, Single-Stranded DNA, Tertiary Protein Structure, Animals, Xenopus
Source:Nucleic Acids Research
ISSN:0305-1048
Publisher:Oxford University Press (U.K.)
Volume:40
Number:15
Page Range:7492-7506
Date:1 August 2012
Official Publication:https://doi.org/10.1093/nar/gks355
PubMed:View item in PubMed

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