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XB-ART-46245
Nucleic Acids Res. August 1, 2012; 40 (15): 7492-506.

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

Mayr F , Schütz A , Döge N , 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.

PubMed ID: 22570413
PMC ID: PMC3424542
Article link: Nucleic Acids Res.

Genes referenced: c9orf3 dicer1 lin28a lin28b psmb4 tdrd6 tgfbi usp9x zcchc11


References:
Amarasinghe, 2000, Pubmed[+]


Article Images: [+] show captions

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