A 1.1-Mb Segmental Deletion on the X Chromosome Causes Meiotic Failure in Male Mice
BIOLOGY OF REPRODUCTION
Authors: Zhou, Jian; McCarrey, John R.; Wang, P. Jeremy
Abstract
The mammalian X chromosome contains a large number of multicopy genes that are expressed during spermatogenesis. The roles of these genes during germ cell development and the functional significance of gene multiplication remain mostly unexplored, as the presence of multicopy gene families poses a challenge for genetic studies. Here we report the deletion of a 1.1-Mb segment of the mouse X chromosome that is syntenic with the human Xq22.1 region and contains 20 genes that are expressed predominantly in testis and brain, including three members of the nuclear export factor gene family (Nxf2, Nxf3, and Nxf7) and five copies of preferentially expressed antigen in melanoma-like 3 (Pramel3). We have shown that germline-specific Cre/loxP-mediated deletion of this 1.1-Mb segment is efficient and causes defective chromosomal synapsis, meiotic arrest, and sterility in male mice. Our results demonstrate that this 1.1-Mb region contains one or more novel X-linked factors that are essential for male meiosis.
Nuclear export factor 3 regulates localization of small nucleolar RNAs
JOURNAL OF BIOLOGICAL CHEMISTRY
Authors: Li, Melissa W.; Sletten, Arthur C.; Lee, Jiyeon; Pyles, Kelly D.; Matkovich, Scot J.; Ory, Daniel S.; Schaffer, Jean E.
Abstract
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.
COA
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