The EMBO Reports

Lemberger, Thomas

doi: 10.1038/s44319-024-00119-4pmid: 38509354

The rise of generative AI will transform scientific publishing but it also poses risks. While AI enables the dissemination of knowledge in computable form, preserving transparency and human values will become even more important for maintaining trust in the scientific discourse.

Gannon, Frank

doi: 10.1038/s44319-024-00079-9pmid: 38316901

We need better post-approval monitoring and reporting to assess the efficiency of new cancer therapies in the real world beyond clinical trials.[graphic not available: see fulltext]

Jacobs, Howy

doi: 10.1038/s44319-024-00087-9pmid: 38332151

The Covid pandemic is long past, but its detrimental effects on science still linger.[graphic not available: see fulltext]

Krink, Nicolas; Nikel, Pablo Iván; Beisel, Chase L

doi: 10.1038/s44319-024-00086-wpmid: 38347223

Join us on a journey through the complex and ever-expanding universe of CRISPR approaches for genome editing in bacteria. Discover what is available, current technical challenges, successful implementation of these tools and the regulatory framework around their use.[graphic not available: see fulltext]

Sawai, Tsutomu; Kataoka, Masanori

doi: 10.1038/s44319-024-00099-5pmid: 38438801

The recent generation of brain organoids from human foetal tissue highlights the need for nuanced ethical considerations and international coordination to navigate the complexities of this research and its broader implications for developmental neuroscience and ethical debates.[graphic not available: see fulltext]

Van Minnebruggen, Geert; Lippens, Saskia

doi: 10.1038/s44319-024-00078-wpmid: 38374202

The rapid pace of technology evolution puts pressure on scientists, research institutes and core facilities to explore and embrace the latest developments. Cooperation and various testing strategies are key to efficiently decide on which platforms are promising and worthwhile to adopt.[graphic not available: see fulltext]

Kuchitsu, Yoshihiko; Taguchi, Tomohiko

doi: 10.1038/s44319-024-00120-xpmid: 38503877

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune pathway has emerged as a critical driver of inflammation in a variety of settings, such as virus infection, cellular stress, tissue damage, and aging. The pathway detects microbial and host-derived double-stranded DNA (dsDNA) in the cytosol and triggers the production of type I interferons and proinflammatory cytokines that help eliminate the invading pathogens. STING is a mobile protein. After its binding to cyclic GMP-AMP, which is generated by cGAS in the presence of cytosolic dsDNA, STING exits the ER, translocates to the Golgi and then to recycling endosomes (REs), finally reaching lysosomes. In the course of its travel, STING recruits TBK1 from the cytosol and triggers type I interferon and proinflammatory responses through the activation of IRF3 and NF-κB at the trans-Golgi network (TGN).

Goh, Kwok Jian; Stubenrauch, Christopher J; Lithgow, Trevor

doi: 10.1038/s44319-024-00111-ypmid: 38467907

The assembly of β-barrel proteins into the bacterial outer membrane is an essential process enabling the colonization of new environmental niches. The TAM was discovered as a module of the β-barrel protein assembly machinery; it is a heterodimeric complex composed of an outer membrane protein (TamA) bound to an inner membrane protein (TamB). The TAM spans the periplasm, providing a scaffold through the peptidoglycan layer and catalyzing the translocation and assembly of β-barrel proteins into the outer membrane. Recently, studies on another membrane protein (YhdP) have suggested that TamB might play a role in phospholipid transport to the outer membrane. Here we review and re-evaluate the literature covering the experimental studies on the TAM over the past decade, to reconcile what appear to be conflicting claims on the function of the TAM.

Oomen, Marlies E; Torres-Padilla, Maria-Elena

doi: 10.1038/s44319-024-00118-5pmid: 38528171

Remnants of transposable elements (TEs) are widely expressed throughout mammalian embryo development. Originally infesting our genomes as selfish elements and acting as a source of genome instability, several of these elements have been co-opted as part of a complex system of genome regulation. Many TEs have lost transposition ability and their transcriptional potential has been tampered as a result of interactions with the host throughout evolutionary time. It has been proposed that TEs have been ultimately repurposed to function as gene regulatory hubs scattered throughout our genomes. In the early embryo in particular, TEs find a perfect environment of naïve chromatin to escape transcriptional repression by the host. As a consequence, it is thought that hosts found ways to co-opt TE sequences to regulate large-scale changes in chromatin and transcription state of their genomes. In this review, we discuss several examples of TEs expressed during embryo development, their potential for co-option in genome regulation and the evolutionary pressures on TEs and on our genomes.

Kotenko, Oleksii; Makovets, Svetlana

doi: 10.1038/s44319-024-00114-9pmid: 38480846

Pif1 family helicases are multifunctional proteins conserved in eukaryotes, from yeast to humans. They are important for the genome maintenance in both nuclei and mitochondria, where they have been implicated in Okazaki fragment processing, replication fork progression and termination, telomerase regulation and DNA repair. While the Pif1 helicase activity is readily detectable on naked nucleic acids in vitro, the in vivo functions rely on recruitment to DNA. We identify the single-stranded DNA binding protein complex RPA as the major recruiter of Pif1 in budding yeast, in addition to the previously reported Pif1-PCNA interaction. The two modes of the Pif1 recruitment act independently during telomerase inhibition, as the mutations in the Pif1 motifs disrupting either of the recruitment pathways act additively. In contrast, both recruitment mechanisms are essential for the replication-related roles of Pif1 at conventional forks and during the repair by break-induced replication. We propose a molecular model where RPA and PCNA provide a double anchoring of Pif1 at replication forks, which is essential for the Pif1 functions related to the fork movement.