Articles in 2021

Mitochondrial respiration relies on five enzymatic complexes that couple electron transport with proton pumping, leading to ATP synthesis. Recent studies have shed new light on the organization, assembly and mechanisms of the respiratory complexes, including the formation of their larger assemblies — respiratory supercomplexes — and their roles in physiology.

Entry of SARS-CoV-2 into host cells is mediated by the interaction between the viral spike protein and its receptor angiotensin-converting enzyme 2, followed by virus–cell membrane fusion. Worldwide research efforts have provided a detailed understanding of this process at the structural and cellular levels, enabling successful vaccine development for a rapid response to the COVID-19 pandemic.

tiRNA-containing extracellular vesicles produced by osteoblasts in the bone marrow are taken up by granulocyte–monocyte progenitors, which promotes their proliferation, increasing host immunity.

Recent studies have revolutionized our understanding of the interplay between mRNA poly(A) tails and the processes of translation and mRNA decay in the cytoplasm. Poly(A) tails interact with dedicated RNA-binding proteins and deadenylases, which together determine the impact of poly(A) tails on gene expression.

Integral membrane proteins make up around one quarter of the human proteome and are highly diverse in topology, biophysical features, structure and function. Their biogenesis involves multiple pathways for membrane targeting, insertion into the lipid bilayer, folding and assembly with other subunits. Recent biochemical and structural analyses have provided new insights into these mechanisms.

An amino acid substitution found in a ribosomal protein in archaea can increase translation fidelity and lifespan in metazoans.

DNA polymerase theta (Polθ)-mediated end joining is a recently characterized DNA repair pathway that functions in various cellular contexts to repair DNA double-strand breaks that are not repaired by other pathways. Polθ-mediated end joining both helps maintain the genome and causes genome instability, and is an emerging therapeutic target in cancer.

Dietary restriction in rodents and non-human primates affects key nutrient-sensing signalling pathways to increase healthspan and lifespan. This Review discusses these geroprotective mechanisms and recent insights suggesting that dietary restriction results in similar molecular and metabolic changes in humans, contributing to the prevention of ageing-associated diseases.

Machine learning is becoming a widely used tool for the analysis of biological data. However, for experimentalists, proper use of machine learning methods can be challenging. This Review provides an overview of machine learning techniques and provides guidance on their applications in biology.

This Review discusses our current understanding of cell cycle regulation, the functions of cell cycle checkpoints and how disruption of these finely tuned mechanisms is associated with cancer. Insights into these regulatory mechanisms are creating new opportunities for the treatment of cancer.

Xu et al. report engineering a compact version of Cas that can be useful for a broad range of genome engineering applications in mammalian cells.

Tau oligomers bind to m⁶A-modified RNA transcripts in the cytoplasm via the linker RNA-binding protein HNRNPA2B1; such complexes are found in individuals with Alzheimer disease and are part of a stress response that represses translation.

Deficiency in the protein kinase ATM — a master regulator of double-strand DNA breaks and stress responses — causes ataxia telangiectasia (A-T). Recent studies link A-T with other neurodegenerative disorders, and implicate reactive oxygen species, mitochondrial dysfunction, defects in proteostasis and metabolism, and increased poly(ADP-ribosyl)ation in the aetiology of A-T.

Base excision repair promotes transcriptional noise, which likely increases cell responsiveness to cell-type-specification cues.

In cells, microtubules are dynamically assembled and disassembled at their growing (plus) tips. Recent insights into microtubule plus tip organization now pave the way for understanding the regulation of microtubule dynamics and for addressing how these dynamics allow microtubules to fulfil their vast repertoire of cellular functions.

Polycomb repressive complex 1 (PRC1) and PRC2 are important gene regulators in various physiological contexts, especially in development. Recent studies have uncovered the molecular mechanisms that enable mammalian PRC1 and PRC2 to identify their genomic target sites, modify chromatin properties and control transcription.

Drawing from his personal experience, Neville Sanjana highlights how open science benefits academic careers.

Garabedian et al. developed designer biomolecular condensates serving as tools for flexible interrogation and temporal regulation of cell functions.

In this Comment, the authors draw attention to the role of partial order in biomolecular condensates and propose that cooperative, ordered interactions between condensate components could underlie the formation and function of these diverse macromolecular assemblies.

Suppressing ovulation protects against chromosomal abnormalities in ageing mouse oocytes, which can be partly explained by increasing REC8–cohesin retention on chromosomes.