@article{d8cb4235da2042c49d8100df8e31bc52,
title = "Molecular basis for interaction of let-7 MicroRNAs with Lin28",
abstract = "MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression. Among these, members of the let-7 miRNA family control many cell-fate determination genes to influence pluripotency, differentiation, and transformation. Lin28 is a specific, posttranscriptional inhibitor of let-7 biogenesis. We report crystal structures of mouse Lin28 in complex with sequences from let-7d, let-7-f1, and let-7g precursors. The two folded domains of Lin28 recognize two distinct regions of the RNA and are sufficient for inhibition of let-7 in vivo. We also show by NMR spectroscopy that the linker connecting the two folded domains is flexible, accommodating Lin28 binding to diverse let-7 family members. Protein-RNA complex formation imposes specific conformations on both components that could affect downstream recognition by other processing factors. Our data provide a molecular explanation for Lin28 specificity and a model for how it regulates let-7.",
author = "Yunsun Nam and Casandra Chen and Gregory, {Richard I.} and Chou, {James J.} and Piotr Sliz",
note = "Funding Information: We thank Stephen C. Harrison for discussion and critical review of the manuscript, members of the Chou Lab for discussion about NMR experiments, Janet Iwasa for help with design of Figure 7 , George Q. Daley for the pri-miR constructs for in vivo processing assays, Thomas Tuschl for Dicer expression construct, Katarzyna Szatkowski for technical assistance, and Elizabeth O'Day for participation during the early stages of the project. This work is based upon research conducted at the Advanced Photon Source (Northeastern Collaborative Access Team beamlines) and Brookhaven National Laboratory (beamline X25). This work was partially supported by Center for Molecular and Cellular Dynamics at Harvard Medical School, by NIH grant 5U54GM094608, and by postdoctoral fellowships to Y.N. from the Damon Runyon Cancer Research Foundation (DRG-#1953-07) and the Charles A. King Trust, N.A., Bank of America, Co-Trustee. Y.N. performed experiments. C.C. provided technical assistance with experiments. R.G. provided the Lin28 clone and participated in discussions. J.C. helped with NMR spectroscopy. Y.N. and P.S. designed and interpreted experiments and prepared the manuscript. ",
year = "2011",
month = nov,
day = "23",
doi = "10.1016/j.cell.2011.10.020",
language = "English (US)",
volume = "147",
pages = "1080--1091",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}