Developmental roles and molecular mechanisms of Asterix/GTSF1

Maintenance of germline genomic integrity is critical for the survival of animal species. Consequently, many cellular and molecular processes have evolved to ensure genetic stability during the production of gametes. Here, we describe the discovery, characterization, and emerging molecular mechanisms of the protein Asterix/Gametocyte-specific factor 1 (GTSF1), an essential gametogenesis factor that is conserved from insects to humans. Beyond its broad importance for healthy germline development, Asterix/GTSF1 has more specific functions in the Piwi-interacting RNA (piRNA)-RNA interference pathway. There, it contributes to the repression of otherwise deleterious transposons, helping to ensure faithful transmission of genetic information to the next generation. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications

Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.

The Piwi-interacting RNA (piRNA) pathway safeguards genomic integrity by silencing transposable elements (transposons) in the germline. While Piwi is the central piRNA factor, others including Asterix/Gtsf1 have also been demonstrated to be critical for effective silencing. Here, using enhanced crosslinking and immunoprecipitation (eCLIP) with a custom informatic pipeline, we show that Asterix/Gtsf1 specifically binds tRNAs in cellular contexts. We determined the structure of mouse Gtsf1 by NMR spectroscopy and identified the RNA-binding interface on the protein's first zinc finger, which was corroborated by biochemical analysis as well as cryo-EM structures of Gtsf1 in complex with co-purifying tRNA. Consistent with the known dependence of long terminal repeat (LTR) retrotransposons on tRNA primers, we demonstrate that LTR retrotransposons are, in fact, preferentially de-repressed in Asterix mutants. Together, these findings link Asterix/Gtsf1, tRNAs, and LTR retrotransposon silencing and suggest that Asterix exploits tRNA dependence to identify transposon transcripts and promote piRNA silencing

SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease.

We studied plasma antibody responses of 35 patients about 1 month after SARS-CoV-2 infection. Titers of antibodies binding to the viral nucleocapsid and spike proteins were significantly higher in patients with severe disease. Likewise, mean antibody neutralization titers against SARS-CoV-2 pseudovirus and live virus were higher in the sicker patients, by ∼5-fold and ∼7-fold, respectively. These findings have important implications for those pursuing plasma therapy, isolation of neutralizing monoclonal antibodies, and determinants of immunity

Complete Structural Model of Escherichia coli RNA Polymerase from a Hybrid Approach

A combination of structural approaches yields a complete atomic model of the highly biochemically characterized Escherichia coli RNA polymerase, enabling fuller exploitation of E. coli as a model for understanding transcription

siRNAs at RISC

AbstractA recent report (Ma et al., 2004) describes the crystal structure of a “mini-siRNA” bound to a PAZ domain