@article{33c7e36f25c94956a5aa3962cbe1c557,
title = "RNA Specificity and Autoregulation of DDX17, a Modulator of MicroRNA Biogenesis",
abstract = "DDX17, a DEAD-box ATPase, is a multifunctional helicase important for various RNA functions, including microRNA maturation. Key questions for DDX17 include how it recognizes target RNAs and influences their structures, as well as how its ATPase activity may be regulated. Through crystal structures and biochemical assays, we show the ability of the core catalytic domains of DDX17 to recognize specific sequences in target RNAs. The RNA sequence preference of the catalytic core is critical for DDX17 to directly bind and remodel a specific region of primary microRNAs 3′ to the mature sequence, and consequently enhance processing by Drosha. Furthermore, we identify an intramolecular interaction between the N-terminal tail and the DEAD domain of DDX17 to have an autoregulatory role in controlling the ATPase activity. Thus, we provide the molecular basis for how cognate RNA recognition and functional outcomes are linked for DDX17.",
keywords = "ATPase, DDX17, DEAD-box helicase, DGCR8, Drosha, Microprocessor, RNA, microRNA, p72, pri-miRNA",
author = "Ngo, {Tri D.} and Partin, {Alexander C.} and Yunsun Nam",
note = "Funding Information: We thank the support from the Cecil H. and Ida Green Center Training Program in Reproductive Biology Sciences Research and also members of the Structural Biology Laboratory at UT Southwestern for help with synchrotron data collection. Y.N. is a Southwestern Medical Foundation Scholar in Biomedical Research (Endowed Scholar Program at UT Southwestern), a Pew Scholar in the Biomedical Sciences (27339), and a Packard Fellow (2013-39275). This study was supported by grants from the NIH NIGMS (R01GM122960), the Welch Foundation (I-1851-20170325), and the Cancer Prevention Research Institute of Texas (R1221). The use of SBC 19ID beamline at the Advanced Photon Source is supported by the United States Department of Energy contract DE-AC02-06CH11357. T.D.N. and Y.N. designed experiments. T.D.N. carried out most of the experiments, including determining and refining the crystal structures. A.C.P. performed qPCR experiments and assisted with biochemical assays. T.D.N. A.C.P. and Y.N. wrote the manuscript. The authors declare no competing interests. Funding Information: We thank the support from the Cecil H. and Ida Green Center Training Program in Reproductive Biology Sciences Research and also members of the Structural Biology Laboratory at UT Southwestern for help with synchrotron data collection. Y.N. is a Southwestern Medical Foundation Scholar in Biomedical Research (Endowed Scholar Program at UT Southwestern), a Pew Scholar in the Biomedical Sciences ( 27339 ), and a Packard Fellow ( 2013-39275 ). This study was supported by grants from the NIH NIGMS ( R01GM122960 ), the Welch Foundation ( I-1851-20170325 ), and the Cancer Prevention Research Institute of Texas ( R1221 ). The use of SBC 19ID beamline at the Advanced Photon Source is supported by the United States Department of Energy contract DE-AC02-06CH11357 . Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = dec,
day = "17",
doi = "10.1016/j.celrep.2019.11.059",
language = "English (US)",
volume = "29",
pages = "4024--4035.e5",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}