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  • The oncoprotein MYC undergoes multimerization to limit transcription–replication conflicts, thereby reducing the formation of DNA double-strand breaks in cancer cells.

    • Eytan Zlotorynski
    Research Highlight
  • Membraneless organelles (MLOs) contribute to intracellular compartmentalization and to various cellular processes. This Review provides a guide to MLOs involved in gene regulation in eukaryotes, discussing their assembly, structure, roles in transcription, RNA processing and translation — particularly in stress conditions — and their disease relevance.

    • Tetsuro Hirose
    • Kensuke Ninomiya
    • Tomohiro Yamazaki
    Review Article
  • In this World View, Felicity Davis discusses how efforts surrounding diversity, equity and inclusion (DEI) often serve to tick a mandatory box, rather than delivering a meaningful change in the DEI space.

    • Felicity M. Davis
    World View
  • Bera et al. demonstrate that increased viscosity of the surrounding fluid promotes cell migration, supporting tumour cell dissemination and tissue colonization in vivo.

    • Paulina Strzyz
    Research Highlight
  • The genome contains various non-coding regulatory elements, including silencers of gene expression. Recent progress in the identification and characterization of silencers has considerably deepened our understanding of their function, and has shed light on the potential relevance of targeting silencers in therapy for hereditary diseases.

    • Baoxu Pang
    • Jan H. van Weerd
    • Michael P. Snyder
    Review Article
  • Malka et al. uncover thousands of 5′ uncapped and polyadenylated transcripts (5′ UPTs) and describe their biogenesis through the alternative polyadenylation pathway. 5′ UPTs contribute to the proteome as non-canonical peptides with likely diverse biological functions.

    • Lisa Heinke
    Research Highlight
  • Reyes et al. show that fibroblasts with properties of cellular senescence are present in healthy epithelial tissues and — by upregulating the senescence associated secretory phenotype (SASP) — they support stem-cell function and tissue repair.

    • Paulina Strzyz
    Research Highlight
  • Giovanni D’Angelo and Gioele La Manno present the concept of lipotypes, and suggest that lipid composition is an important regulator of cell fate.

    • Giovanni D’Angelo
    • Gioele La Manno
  • AMP-activated protein kinase (AMPK) is a cellular energy sensor canonically activated by increases in AMP/ADP to ATP ratios. Recent advances revealed several non-canonical pathways for AMPK activation, including roles of calcium, nutrients and metabolites, as well as DNA and lysosome damage, providing novel insights into the pathology of AMPK in cancer, metabolic disease, fibrosis and inflammation.

    • Gregory R. Steinberg
    • D. Grahame Hardie
    Review Article
  • Selective autophagy engages several cargo receptors that target specific, potentially toxic, content (damaged organelles, protein aggregates, pathogens) for lysosomal degradation. Understanding of the mechanisms governing this process in mammals has expanded in recent years, opening the prospects for enhancing selective autophagy to boost cellular quality control capabilities.

    • Jose Norberto S. Vargas
    • Maho Hamasaki
    • Tamotsu Yoshimori
    Review Article
  • Recent studies have expanded our understanding of the mechanisms and functions of ubiquitylation. Pathogens rewrite ubiquitylation to promote infection through unconventional ubiquitylation involving lipids and sugars, and structural studies have revealed that ubiquitin functions involve elaborate multivalent interactions that regulate transcription or protein degradation.

    • Ivan Dikic
    • Brenda A. Schulman
    Review Article
  • This Comment draws attention to cellular protrusions as a source of extracellular vesicles (EVs). These protrusion-derived vesicles expand the repertoire of EVs, impacting current nomenclature and our understanding of EV functions in inter-cellular communication.

    • Gisela D’Angelo
    • Graça Raposo
    • Shiro Suetsugu
  • Liming Sun brings to attention paper by Li et al. (2012) reporting that necroptosis kinases, RIPK1 and RIPK3, form functional amyloids that regulate cell death signalling.

    • Liming Sun
    Journal Club
  • Zheng et al. show that calcium transients at the endoplasmic reticulum surface trigger condensation of FIP200 and the formation of ULK1 assemblies for autophagosome biogenesis.

    • Paulina Strzyz
    Research Highlight
  • Alternative splicing substantially contributes to proteomic complexity in multicellular eukaryotes and regulates various physiological and pathological processes, including cell differentiation, neuron self-avoidance, cancer and autism spectrum disorders. Recent advances paved the way to clinical use of alternative splicing-based therapies for hereditary diseases.

    • Luciano E. Marasco
    • Alberto R. Kornblihtt
    Review Article