@article{2a5c50a00a3b45aca03f604aaae1dac4,
title = "Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1",
abstract = "Post-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri-mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its downstream processing. Our results highlight terminal loop RNA recognition by RBPs as a potential general principle of miRNA biogenesis and regulation.",
author = "Hamed Kooshapur and Choudhury, {Nila Roy} and Bernd Simon and Max M{\"u}hlbauer and Alexander Jussupow and Noemi Fernandez and Jones, {Alisha N.} and Andre Dallmann and Frank Gabel and Carlo Camilloni and Gracjan Michlewski and Caceres, {Javier F.} and Michael Sattler",
note = "Funding Information: We thank Marianne Keith (MRC HGU, University of Edinburgh) for Immunofluorescence data, Robert Janowski for collecting the X-ray diffraction data, and Ralf Stehle for help with in-house SAXS measurements. We are grateful to the beamline staff at DESY (Hamburg) and Anne Martel at ILL (Grenoble) for support with SAXS and SANS measurements, respectively. We acknowledge the use of the X-ray crystallography platform at the Helmholtz Zentrum M{\"u}nchen, NMR access at the Bavarian NMR Center and SAXS measurements at the facility of the SFB1035 at Department Chemie, Technical University of Munich. This work was supported by the Deutsche For-schungsgemeinschaft through grants SFB1035 and GRK1721 (to M.S.), MRC core funding and the Wellcome Trust (Grant 095518/Z/11/Z to J.F.C.), Medical Research Council Career Development Award (G10000564 to G.M.). Wellcome Trust Center Core Grants (077707 and 092076 to G.M.). M.M., A.J., and C.C. acknowledge the support of the Technical University of Munich—Institute for Advanced Study, funded by the German Excellence Initiative and the European Union Seventh Framework Programme under grant agreement n° 291763. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-04871-9",
language = "English (US)",
volume = "9",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}