Nuclear export factor 3 regulates localization of small nucleolar RNAs.

Autor: Li MW; Diabetes Research Center, Department of Medicine, St. Louis, Missouri 63110., Sletten AC; Diabetes Research Center, Department of Medicine, St. Louis, Missouri 63110., Lee J; Diabetes Research Center, Department of Medicine, St. Louis, Missouri 63110., Pyles KD; Diabetes Research Center, Department of Medicine, St. Louis, Missouri 63110., Matkovich SJ; Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110., Ory DS; Diabetes Research Center, Department of Medicine, St. Louis, Missouri 63110., Schaffer JE; Diabetes Research Center, Department of Medicine, St. Louis, Missouri 63110. Electronic address: jschaff@wustl.edu.
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2017 Dec 08; Vol. 292 (49), pp. 20228-20239. Date of Electronic Publication: 2017 Oct 11.
DOI: 10.1074/jbc.M117.818146
Abstrakt: Small nucleolar RNAs (snoRNAs) guide chemical modifications of ribosomal and small nuclear RNAs, functions that are carried out in the nucleus. Although most snoRNAs reside in the nucleolus, a growing body of evidence indicates that snoRNAs are also present in the cytoplasm and that snoRNAs move between the nucleus and cytoplasm by a mechanism that is regulated by lipotoxic and oxidative stress. Here, in a genome-wide shRNA-based screen, we identified nuclear export factor 3 (NXF3) as a transporter that alters the nucleocytoplasmic distribution of box C/D snoRNAs from the ribosomal protein L13a ( Rpl13a ) locus. Using RNA-sequencing analysis, we show that NXF3 associates not only with Rpl13a snoRNAs, but also with a broad range of box C/D and box H/ACA snoRNAs. Under homeostatic conditions, gain- or loss-of-function of NXF3, but not related family member NXF1, decreases or increases cytosolic Rpl13a snoRNAs, respectively. Furthermore, treatment with the adenylyl cyclase activator forskolin diminishes cytosolic localization of the Rpl13a snoRNAs through a mechanism that is dependent on NXF3 but not NXF1. Our results provide evidence of a new role for NXF3 in regulating the distribution of snoRNAs between the nuclear and cytoplasmic compartments.
(© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze: MEDLINE