PAPAS promotes differentiation of mammary epithelial cells and suppresses breast carcinogenesis.

Extensive remodeling of the female mammary epithelium during development and pregnancy has been linked to cancer susceptibility. The faithful response of mammary epithelial cells (MECs) to hormone signaling is key to avoiding breast cancer development. Here, we show that lactogenic differentiation of murine MECs requires silencing of genes encoding ribosomal RNA (rRNA) by the antisense transcript PAPAS. Accordingly, knockdown of PAPAS derepresses rRNA genes, attenuates the response to lactogenic hormones, and induces malignant transformation. Restoring PAPAS levels in breast cancer cells reduces tumorigenicity and lung invasion and activates many interferon-regulated genes previously linked to metastasis suppression. Mechanistically, PAPAS transcription depends on R-loop formation at the 3' end of rRNA genes, which is repressed by RNase H1 and replication protein A (RPA) overexpression in breast cancer cells. Depletion of PAPAS and upregulation of RNase H1 and RPA in human breast cancer underpin the clinical relevance of our findings.

Navigating the Landscape: A Comprehensive Review of Current Virus Databases.

Viruses are abundant and diverse entities that have important roles in public health, ecology, and agriculture. The identification and surveillance of viruses rely on an understanding of their genome organization, sequences, and replication strategy. Despite technological advancements in sequencing methods, our current understanding of virus diversity remains incomplete, highlighting the need to explore undiscovered viruses. Virus databases play a crucial role in providing access to sequences, annotations and other metadata, and analysis tools for studying viruses. However, there has not been a comprehensive review of virus databases in the last five years. This study aimed to fill this gap by identifying 24 active virus databases and included an extensive evaluation of their content, functionality and compliance with the FAIR principles. In this study, we thoroughly assessed the search capabilities of five database catalogs, which serve as comprehensive repositories housing a diverse array of databases and offering essential metadata. Moreover, we conducted a comprehensive review of different types of errors, encompassing taxonomy, names, missing information, sequences, sequence orientation, and chimeric sequences, with the intention of empowering users to effectively tackle these challenges. We expect this review to aid users in selecting suitable virus databases and other resources, and to help databases in error management and improve their adherence to the FAIR principles. The databases listed here represent the current knowledge of viruses and will help aid users find databases of interest based on content, functionality, and scope. The use of virus databases is integral to gaining new insights into the biology, evolution, and transmission of viruses, and developing new strategies to manage virus outbreaks and preserve global health.

The International Virus Bioinformatics Meeting 2022.

The International Virus Bioinformatics Meeting 2022 took place online, on 23-25 March 2022, and has attracted about 380 participants from all over the world. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The participants created a highly interactive scientific environment even without physical face-to-face interactions. This meeting is a focal point to gain an insight into the state-of-the-art of the virus bioinformatics research landscape and to interact with researchers in the forefront as well as aspiring young scientists. The meeting featured eight invited and 18 contributed talks in eight sessions on three days, as well as 52 posters, which were presented during three virtual poster sessions. The main topics were: SARS-CoV-2, viral emergence and surveillance, virus-host interactions, viral sequence analysis, virus identification and annotation, phages, and viral diversity. This report summarizes the main research findings and highlights presented at the meeting.