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Nucleoli are the sites of ribosome-subunit biogenesis, but recent large-scale proteomics analyses and other studies have revealed further cellular functions, including cell-cycle control, stress responses and coordination of the processing and maturation of other classes of ribonucleoprotein in addition to the ribosomal class.

Using a previously developed method, Singer and co-workers have now labeled RNA transcripts and quantitatively measured the synthesis of RNA in living cells. They find that only a small fraction of the RNA polymerases that bind the promoter actually produce messenger RNA. They also observed much faster elongation than previously reported, along with frequent long pauses.

A method for performing quantitative proteomics experiments in Caenorhabditis elegans using stable-isotope labeling with amino acids in cell culture (SILAC) is described. The authors used the method to identify heat shock–responsive proteins in worms. Also in this issue, Fredens et al. describe a very similar method.

Glutamine can feed into the TCA cycle as a fuel for oxidative phosphorylation and thereby can affect metabolic pathways in lymphocytes. Yet here the authors show that glutamine serves predominantly as a signalling molecule that sustains cMyc expression to control NK cell metabolism and effector function.

The C. elegans PIWI protein PRG-1 resides in the membraneless organelle P granule. Here, the authors identify the constitutive P granule protein DEPS-1 as an interactor of PRG-1 and show its function in piRNA-dependent silencing. DEPS-1 and PRG-1 form elongated condensates in vivo.

Fgf4 is a critical signal driving embryonic stem cell (ESC) exit from pluripotency and differentiation. Here the authors identify EPHA2 as a target of FGF4 signalling in ESCs, and show that EPHA2-EFNA1 signalling promotes pluripotent gene expression and suppresses commitment through repression of ERK1/2 activation.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The Sm proteins are a conserved family that form the core of the small nuclear ribonucleoprotein particles (snRNPs), which are involved in RNA splicing. There are seven Sm proteins in all, and they can form three stable sub-complexes. The crystal structures of two of these sub-complexes have now been solved, giving an insight into organization of the Sm core domain, and how it might bind RNA.

Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease.

Advances in mass spectrometry-based proteomics are enabling the multidimensional analysis of protein properties such as abundance, localization, post-translational modifications and interactions for thousands of proteins. Complemented by new tools for data analysis and integration, these advances are transforming our understanding of various biological processes.

Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

Cantrell and colleagues perform a comparative quantitative mass spectrometric analysis of the proteomes of naïve and activated CD4⁺ and CD8⁺ T cells. Proteomes are dynamically regulated and mTORC1 inhibition leads to differential consequences depending on cell state.

Cardelino leverages variant information from single-cell RNA-seq data for inferring clonal tree configuration and mapping cells to their clone of origin.

Loss of the ribosome-rescue factor Pelo in a subset of mouse epidermal stem cells results in hyperproliferation and altered differentiation of these cells.

In differentiating cells, ERK activation shifts from transient to sustained. Quantitative proteomics reveals that, during differentiation, dynamic changes in ERK-interacting proteins regulate the pathway at several levels and by different mechanisms, suggesting a distributed control mechanism for the ERK pathway.

Proteomic profiling can provide new insight into the cellular regulation of effector functions. Cantrell and colleagues report discordant mRNA profiles and protein profiles in activated CD8⁺ T cells and reveal new roles for mTORC1 in regulating the function of cytotoxic T lymphocytes.

An RNAi screen of protein phosphatases identifies PP2A–B55α as the main mitotic exit phosphatase in human cells. After mitosis, PP2A–B55α depletion delays the reassembly of the nuclear envelope and Golgi and the decondensation of chromatin.

Abnormalities in the control of intracellular calcium are involved in several forms of inherited arrhythmias. The genetic mutations that cause these abnormalities have generated much research interest in the past decade. Here, Venetucci et al. provide an overview of the structural organization and the function of calcium-handling proteins and describe the mechanisms by which mutations determine the various clinical phenotypes of calcium channelopathies.

The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.

Analysis of the available human small ubiquitin-like modifier (SUMO) proteomics data provided evidence for the sumoylation of thousands of proteins and residues, and clustered the sumoylated proteins into functional networks. Sumoylation is a frequent modification, occurring mostly on nuclear proteins, with functions including transcription, mRNA processing and the DNA-damage response.

Large-scale approaches have linked protein phosphatase function to a multitude of nuclear processes, such as the DNA-damage response, cell-cycle progression and gene regulation. In addition, proteomics techniques have enabled the identification of new components of multiprotein phosphatase complexes, such as targeting and regulatory subunits.