期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 292, 期 49, 页码 20228-20239出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M117.818146
关键词
intracellular trafficking; molecular cell biology; nuclear transport; RNA transport; small nucleolar RNA (snoRNA)
资金
- NCI [P30 CA91842]
- ICTS/CTSA from the NCRR [UL1 TR000448]
- National Institutes of Health
- National Institutes of Health Roadmap for Medical Research
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.
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