| First Author | Desjardins A | Year | 2012 |
| Journal | Nucleic Acids Res | Volume | 40 |
| Issue | 4 | Pages | 1767-77 |
| PubMed ID | 22013165 | Mgi Jnum | J:197740 |
| Mgi Id | MGI:5494394 | Doi | 10.1093/nar/gkr808 |
| Citation | Desjardins A, et al. (2012) Importance of the NCp7-like domain in the recognition of pre-let-7g by the pluripotency factor Lin28. Nucleic Acids Res 40(4):1767-77 |
| abstractText | The pluripotency factor Lin28 is a highly conserved protein comprising a unique combination of RNA-binding motifs, an N-terminal cold-shock domain and a C-terminal region containing two retroviral-type CCHC zinc-binding domains. An important function of Lin28 is to inhibit the biogenesis of the let-7 family of microRNAs through a direct interaction with let-7 precursors. Here, we systematically characterize the determinants of the interaction between Lin28 and pre-let-7 g by investigating the effect of protein and RNA mutations on in vitro binding. We determine that Lin28 binds with high affinity to the extended loop of pre-let-7 g and that its C-terminal domain contributes predominantly to the affinity of this interaction. We uncover remarkable similarities between this C-terminal domain and the NCp7 protein of HIV-1, not only in terms of primary structure but also in their modes of RNA binding. This NCp7-like domain of Lin28 recognizes a G-rich bulge within pre-let-7 g, which is adjacent to one of the Dicer cleavage sites. We hypothesize that the NCp7-like domain initiates RNA binding and partially unfolds the RNA. This partial unfolding would then enable multiple copies of Lin28 to bind the extended loop of pre-let-7 g and protect the RNA from cleavage by the pre-microRNA processing enzyme Dicer. |
