Reviews & Analysis

Autophagy can serve both tumour-suppressive and tumour-promoting roles, often depending on disease stage and mutational background. Recent findings have advanced our understanding of these seemingly opposing roles of autophagy in cancer cells themselves and in the tumour microenvironment.

Mechanical cues from the extracellular matrix (ECM) regulate cell fate and behaviour through cell–ECM mechanotransduction. Studies of cell–ECM mechanotransduction have largely focused on cells cultured in 2D, and only recently have we begun to unravel how these processes occur in 3D — a context native to many cells in vivo.

CRISPR-based genetic screens are providing new insights into the consequences of deficiencies in DNA damage response and repair pathways. These include insights into the regulation of homologous recombination and of replication stress and their crosstalk with other repair pathways, into novel cancer therapies and into the basis of cancer-drug resistance.

Extracellular vesicles (EVs) have emerged as important players in intercellular communication, carrying proteins, lipids, nucleic acids and various signalling molecules between cells. Unravelling how these different cargoes are sorted into EVs in a regulated and context-specific manner is essential to understanding the specificity of EV-mediated signalling.

Ribosome biogenesis, including ribosomal RNA (rRNA) production, occurs in the nucleolus. Recent studies have revealed how the integrity and copy number of rRNA genes is maintained through a unique recombination system, how rRNA transcription is regulated and how phase separation orchestrates nucleolus function.

Metabolites are generally viewed as intermediates or products of metabolism. However, many metabolites are also signalling molecules that regulate metabolic reactions and other processes in development, homeostasis and disease. As such, metabolites can confer adaptive responses to environmental changes.

The inability of the mammalian central nervous system to functionally regenerate after injury is largely attributable to the limited capacity of injured neurons to regrow axons. In the spinal cord, recent work on the mechanisms restricting axon regrowth suggests new therapeutic avenues to promote functional recovery after damage.

This Consensus Statement addresses the definition, nomenclature and classification of long non-coding RNAs, and provides a shared viewpoint on their features and functions. The authors also discuss research challenges and provide recommendations to advance our understanding of long non-coding RNAs.