Nonclassical nuclear localization signals mediate nuclear import of CIRBP.

The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)-rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these nonclassical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.

Effect of probiotics on vaginal Ureaplasma parvum in women suffering from unexplained infertility.

RESEARCH QUESTION: Does oral probiotic supplementation influence the relative abundance of different vaginal microbiota in women experiencing infertility? DESIGN: A prospective, monocentric randomized controlled trial. To study the influence of probiotics on infertility, 80 patients with primary or secondary infertility were included. Patients were assigned to either a probiotic treatment or a control group. Participants in the treatment group (n = 40) took one sachet (2 g) a day of a defined probiotic supplement limiting Lactobacillus strains. Patients in the control group did not receive any additional probiotic supplements. Vaginal samples were taken on day 20 of the menstrual cycle and 4 weeks later, on day 20, of the consecutive cycle. Subsequently, 16s rRNA gene analysis of the vaginal samples was conducted. RESULTS: After the intervention phase, no effects on alpha diversity resulting from treatment could be observed. The between sample diversity of different women (beta diversity) at baseline had no effects of age, treatment group or body mass index. Primary or secondary sterility, however, had a significant effect on community. Three clusters (Lactobacillus crispatus, Lactobacillus iners and Lactobacillus gasseri) were identified as the leading representatives. Furthermore, patients treated with probiotics showed limited growth of Ureaplasma parvum compared with the control group (P = 0.021). CONCLUSIONS: This study points to a possible protective effect of probiotic supplements on the vaginal microbiota. It is tempting to speculate that this effect assists in containing the growth of non-beneficial bacteria and helps to prevent or cure a dysbiotic vaginal flora.