A nanobody targeting the LIN28:let-7 interaction fragment of TUT4 blocks uridylation of let-7.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32060122.
- Also identified by DOI 10.1073/pnas.1919409117 and PMC identifier 7060709.
- Licence recorded as CC BY-NC-ND.
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Abstract
The LIN28:pre-let-7:TUTase ternary complex regulates pluripotency and oncogenesis by controlling processing of the let-7 family of microRNAs. The complex oligouridylates the 3' ends of pre-let-7 molecules, leading to their degradation via the DIS3L2 exonuclease. Previous studies suggest that components of this complex are potential therapeutic targets in malignancies that aberrantly express LIN28. In this study we developed a functional epitope selection approach to identify nanobody inhibitors of the LIN28:pre-let-7:TUT4 complex. We demonstrate that one of the identified nanobodies, Nb-S2A4, targets the 106-residue LIN28:let-7 interaction (LLI) fragment of TUT4. Nb-S2A4 can effectively inhibit oligouridylation and monouridylation of pre-let-7g in vitro. Expressing Nb-S2A4 allows maturation of the let-7 species in cells expressing LIN28, highlighting the therapeutic potential of targeting the LLI fragment.
Medical subject headings
- DNA-Binding Proteins
- MicroRNAs
- RNA 3' End Processing
- Single-Domain Antibodies