Coevolution of RtcB and Archease created a multiple-turnover RNA ligase.

RtcB is a noncanonical RNA ligase that joins either 2',3'-cyclic phosphate or 3'-phosphate termini to 5'-hydroxyl termini. The genes encoding RtcB and Archease constitute a tRNA splicing operon in many organisms. Archease is a cofactor of RtcB that accelerates RNA ligation and alters the NTP specificity of the ligase from Pyrococcus horikoshii. Yet, not all organisms that encode RtcB also encode Archease. Here we sought to understand the differences between Archease-dependent and Archease-independent RtcBs so as to illuminate the evolution of Archease and its function. We report on the Archease-dependent RtcB from Thermus thermophilus and the Archease-independent RtcB from Thermobifida fusca. We find that RtcB from T. thermophilus can catalyze multiple turnovers only in the presence of Archease. Remarkably, Archease from P. horikoshii can activate T. thermophilus RtcB, despite low sequence identity between the Archeases from these two organisms. In contrast, RtcB from T. fusca is a single-turnover enzyme that is unable to be converted into a multiple-turnover ligase by Archease from either P. horikoshii or T. thermophilus. Thus, our data indicate that Archease likely evolved to support multiple-turnover activity of RtcB and that coevolution of the two proteins is necessary for a functional interaction.

The levonorgestrel-releasing intrauterine system: its effect on the number of hysterectomies performed in perimenopausal women with uterine fibroids.

This prospective observational study was designed to determine the percentage of hysterectomies avoided following insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) in perimenopausal women with uterine fibroids and a prior indication for surgery. The study also compared the progress of patients using the LNG-IUS with those submitted to hysterectomy, with particular emphasis on the patient's satisfaction with treatment. Sixty perimenopausal patients with uterine fibroids and excessive bleeding referred for hysterectomy were included. After counseling on the possibility of non-surgical treatment, 39 patients opted to use an LNG-IUS while 21 opted for hysterectomy. Continuation of LNG-IUS use and the patient's satisfaction with the chosen procedure were assessed. A secondary analysis evaluated hemoglobin levels, clinical complications, bleeding patterns and uterine volume at ultrasonography over time. After 24 months of follow-up, four of the patients who had opted to use an LNG-IUS were submitted to surgery, while 35 continued using the device, thus avoiding hysterectomy in 89.5% of cases. LNG-IUS users were more satisfied with treatment (p = 0.02) compared to those submitted to hysterectomy. In conclusion, the use of the LNG-IUS enables the number of hysterectomies to be reduced in women with uterine fibroids and is associated with greater satisfaction compared to surgical treatment.