Articles in 2022

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.

Tan and Finkel report a novel phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway that is crucial for lysosome membrane repair.

Integrator is the only metazoan-specific RNA polymerase II (Pol II)-associated large multisubunit complex. Processing of non-coding RNAs by Integrator is essential for their biogenesis, and, at protein-coding genes, Integrator regulates Pol II promoter-proximal pausing and elongation. Consequently, Integrator has diverse roles in development and tumorigenesis.

Cell competition results in stochastic cell turnover or elimination of less fit cells from a tissue. Although cell competition generally supports tissue development and homeostasis, it can also promote malignant growth and is subverted during ageing. Addressing how cell fitness is determined and sensed is being actively pursued.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is important for replication-fork reversal under replication stress, and its inhibition can abolish PARP-inhibitor resistance in cancer cells.

Cell–extracellular matrix (ECM) interactions occur at specialized, multi-protein adhesion complexes, with clustered integrins as the predominant ECM receptors. Progress in characterization of adhesion composition, organization and dynamics in response to force has improved understanding of adhesion maturation and turnover and the relationships between adhesion structures and functions.

Kalkavan et al. show how drug-tolerant persister cells evade apoptosis by release of sublethal cytochrome c and activation of the integrated stress response.

PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with essential roles in germ line development through silencing of transposable elements and in regulation of protein-coding genes. Recent studies have deepened our understanding of the biogenesis and function of piRNAs and their roles in infertility, cancer and neurological diseases in humans.

Podosomes and invadopodia, collectively called ‘invadosomes’, are actin-based structures that drive proteolytic invasion in various physiologically relevant cell types (including osteoclasts, immune cells, endothelial cells and fibroblasts) and in cancer cells. Recent work has expanded our understanding of the architecture and mechanisms of invadosomes, and has revealed their diverse functions beyond matrix degradation.

Microautophagy involves direct engulfment of cytoplasmic components, including proteins and organelles, by lysosomes and late endosomes for degradation. Although it is one of three main types of autophagy — along with macroautophagy and chaperone-mediated autophagy — its mechanisms and physiological roles have only recently begun to emerge.

Leilei Chen describes the discovery that adenosine-to-inosine editing by ADAR1 marks endogenous double-stranded RNA as self, to prevent it from triggering innate immunity.

Bishop and Hawley argue against a direct relationship between changes in mRNA levels and the abundance of the proteins they encode in skeletal muscles in response to exercise.

Fidelity of meiosis in human oocytes can be compromised, leading to egg aneuploidy and impaired embryo development, which increase with advanced maternal age. Recent studies have shed light on the molecular mechanisms underlying aberrant chromosome segregation during oocyte meiosis and the impact of ageing on this process.

Steinhorst et al. show how calcium signal induced by salt stress is ‘decoded’ by plant roots to provide systemic response and to increase salt tolerance.

Transmembrane proteins associate with specific subsets of lipids, which create nano-environments with unique properties. Better understanding of how these nano-environments regulate protein dynamics and function will afford means to control activities of transmembrane proteins, many of which serve essential signalling and transport roles.

Yang, Zhu et al. describe temperature-dependent structural conformations of COOLAIR lncRNA and their impact on flowering time.

Translation reprogramming in plants in response to innate-immunity induction relies on a novel cap-independent translation pathway.

During mammalian development, certain regulatory-gene promoters acquire both histone modifications associated with gene activation and with gene repression (bivalent chromatin), which is key to cell-lineage specification. Recent work has expanded our understanding of the molecular basis of bivalent chromatin and its roles in development and cancer.