An Exportin-1–Dependent Microrna Biogenesis Pathway During Human Cell Quiescence
An Exportin-1–dependent microRNA biogenesis PNAS PLUS pathway during human cell quiescence Ivan Martineza,1,2, Karen E. Hayesa,1, Jamie A. Barra, Abby D. Harolda, Mingyi Xieb, Syed I. A. Bukharic, Shobha Vasudevanc, Joan A. Steitzd,e,f,2, and Daniel DiMaiod,f,g,h aDepartment of Microbiology, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV 26506; bDepartment of Biochemistry and Molecular Biology, University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610; cCancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; dDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536; eHoward Hughes Medical Institute, Yale University, New Haven, CT 06536; fYale Cancer Center, New Haven, CT 06520; gDepartment of Genetics, Yale School of Medicine, New Haven, CT 06510; and hDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06510 Contributed by Joan A. Steitz, May 11, 2017 (sent for review November 14, 2016; reviewed by Judith Campisi, Richard I. Gregory, and Narry Kim) The reversible state of proliferative arrest known as “cellular qui- mature miRNA. Finally, the guide miRNA strand is loaded into escence” plays an important role in tissue homeostasis and stem the RNA-induced silencing complex (RISC) containing one of cell biology. By analyzing the expression of miRNAs and miRNA- four Argonaute proteins and GW182 protein at its core (18–20). processing factors during quiescence in primary human fibroblasts, Recent studies have identified alternative pathways of miRNA we identified a group of miRNAs that are induced during quies- biogenesis in different cell and animal models: pre-miRNA/intron cence despite markedly reduced expression of Exportin-5, a pro- miRNAs (miRtrons), which are Drosha and DGCR8 indepen- tein required for canonical miRNA biogenesis.
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