Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively
| Autor: | Nowak, Jakub Stanislaw, Hobor, Fruzsina, Downie Ruiz Velasco, Angela, Choudhury, Nila Roy, Heikel, Gregory, Kerr, Alastair, Ramos, Andres, Michlewski, Gracjan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Neurons
Pluripotent Stem Cells Poly U RNA Cleavage Base Sequence Recombinant Fusion Proteins Green Fluorescent Proteins RNA-Binding Proteins Cell Differentiation RNA Nucleotidyltransferases Tretinoin Article DNA-Binding Proteins Mice MicroRNAs Gene Expression Regulation Cell Line Tumor Exoribonucleases RNA Precursors Animals Humans Nucleic Acid Conformation Base Pairing HeLa Cells Protein Binding |
| Popis: | Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing. |
| Databáze: | OpenAIRE |
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