Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans.

Piwi-interacting RNAs (piRNAs) constitute a class of small RNAs that bind PIWI proteins and are essential to repress transposable elements in the animal germline, thereby promoting genome stability and maintaining fertility. C. elegans piRNAs (21U RNAs) are transcribed individually from minigenes as precursors that require 5' and 3' processing. This process depends on the PETISCO complex, consisting of four proteins: IFE-3, TOFU-6, PID-3, and ERH-2. We used biochemical and structural biology approaches to characterize the PETISCO architecture and its interaction with RNA, together with its effector proteins TOST-1 and PID-1. These two proteins define different PETISCO functions: PID-1 governs 21U processing, whereas TOST-1 links PETISCO to an unknown process essential for early embryogenesis. Here, we show that PETISCO forms an octameric assembly with each subunit present in two copies. Determination of structures of the TOFU-6/PID-3 and PID-3/ERH-2 subcomplexes, supported by in vivo studies of subunit interaction mutants, allows us to propose a model for the formation of the TOFU-6/PID-3/ERH-2 core complex and its functionality in germ cells and early embryos. Using NMR spectroscopy, we demonstrate that TOST-1 and PID-1 bind to a common surface on ERH-2, located opposite its PID-3 binding site, explaining how PETISCO can mediate different cellular roles.

Low seroprotection rate for meningococcus serogroup C in the adult HIV-1-infected population in Austria.

Current Advisory Committee on Immunization Practices (ACIP) guidelines recommend immunization of all human immunodeficiency virus (HIV)-infected patients against meningitis serotype ACWY due to recent outbreaks of meningitis C in homosexual men in the USA. Implementation of this recommendation in other countries, such as Austria is hindered by the scarce knowledge on the vaccine coverage. In this study the serostatus for meningococcus serogroup C was analyzed in 390 HIV-infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73% were on suppressive antiretroviral therapy, the mean CD4 cell count was 599 cells/µl and immunoglobulin G (IgG) seropositivity was 18% for meningococcus serogroup C. Migrants and patients who had acquired an infection via heterosexual intercourse had a higher chance for meningococcus serogroup C seropositivity. Importantly due to the well-preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. It is assumed that this measure would largely reduce the number of patients at risk for this vaccine-preventable disease.