Nature Reviews Molecular Cell Biology

Ma, Qin; Xu, Dong

doi: 10.1038/s41580-022-00466-xpmid: 35197610

Deep learning has tremendous potential in single-cell data analyses, but numerous challenges and possible new developments remain to be explored. In this commentary, we consider the progress, limitations, best practices and outlook of adapting deep learning methods for analysing single-cell data.

Baumann, Kim

doi: 10.1038/s41580-022-00481-ypmid: 35383337

The transcription factor c-Maf is required for the specification of liver sinusoids and for the maintenance of a specialized sinusoidal network necessary for sustaining hepatocyte function.

Strzyz, Paulina

doi: 10.1038/s41580-022-00475-wpmid: 35296797

Arnold et al. document an alternative tricarboxylic acid cycle that takes place between the mitochondria and the cytosol and that can be adopted in specific cell states.

Zlotorynski, Eytan

doi: 10.1038/s41580-022-00477-8pmid: 35338358

The solid phase of oskar mRNA granules is required for proper Oskar protein synthesis and fruit fly development.

Aktaş, Tuğçe

doi: 10.1038/s41580-022-00470-1pmid: 35264767

Transposons and their host genomes are entangled in an evolutionary arms race, recounts Tuğçe Aktaş.

Ting, Angela H.; Lee, Byron H.

doi: 10.1038/s41580-022-00469-8pmid: 35217851

Ting and Lee describe how the trypanosome base J ‘inspired’ the discovery of the mechanism of active DNA demethylation.

Wing, Casey E.; Fung, Ho Yee Joyce; Chook, Yuh Min

doi: 10.1038/s41580-021-00446-7pmid: 35058649

Efficient and regulated nucleocytoplasmic trafficking of macromolecules to the correct subcellular compartment is critical for proper functions of the eukaryotic cell. The majority of the macromolecular traffic across the nuclear pores is mediated by the Karyopherin-β (or Kap) family of nuclear transport receptors. Work over more than two decades has shed considerable light on how the different Kap family members bring their respective cargoes into the nucleus or the cytoplasm in efficient and highly regulated manners. In this Review, we overview the main features and established functions of Kap family members, describe how Kaps recognize their cargoes and discuss the different ways in which these Kap–cargo interactions can be regulated, highlighting new findings and open questions. We also describe current knowledge of the import and export of the components of three large gene expression machines — the core replisome, RNA polymerase II and the ribosome — pointing out the questions that persist about how such large macromolecular complexes are trafficked to serve their function in a designated subcellular location.

Shvedunova, Maria; Akhtar, Asifa

doi: 10.1038/s41580-021-00441-ypmid: 35042977

Lysine acetylation is a widespread and versatile protein post-translational modification. Lysine acetyltransferases and lysine deacetylases catalyse the addition or removal, respectively, of acetyl groups at both histone and non-histone targets. In this Review, we discuss several features of acetylation and deacetylation, including their diversity of targets, rapid turnover, exquisite sensitivity to the concentrations of the cofactors acetyl-CoA, acyl-CoA and NAD+, and tight interplay with metabolism. Histone acetylation and non-histone protein acetylation influence a myriad of cellular and physiological processes, including transcription, phase separation, autophagy, mitosis, differentiation and neural function. The activity of lysine acetyltransferases and lysine deacetylases can, in turn, be regulated by metabolic states, diet and specific small molecules. Histone acetylation has also recently been shown to mediate cellular memory. These features enable acetylation to integrate the cellular state with transcriptional output and cell-fate decisions.

Cruz Walma, David A.; Chen, Zhuoyao; Bullock, Alex N.; Yamada, Kenneth M.

doi: 10.1038/s41580-021-00448-5pmid: 35079164

Mammalian development demands precision. Millions of molecules must be properly located in temporal order, and their function regulated, to orchestrate important steps in cell cycle progression, apoptosis, migration and differentiation, to shape developing embryos. Ubiquitin and its associated enzymes act as cellular guardians to ensure precise spatio-temporal control of key molecules during each of these important cellular processes. Loss of precision results in numerous examples of embryological disorders or even cancer. This Review discusses the crucial roles of E3 ubiquitin ligases during key steps of early mammalian development and their roles in human disease, and considers how new methods to manipulate and exploit the ubiquitin regulatory machinery — for example, the development of molecular glues and PROTACs — might facilitate clinical therapy.

van Niel, Guillaume; Carter, David R. F.; Clayton, Aled; Lambert, Daniel W.; Raposo, Graça; Vader, Pieter

doi: 10.1038/s41580-022-00460-3pmid: 35260831

Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. They have important roles in numerous physiological and pathological processes, and show considerable promise as novel biomarkers of disease, as therapeutic agents and as drug delivery vehicles. Intriguingly, however, understanding of the cellular and molecular mechanisms that govern the many observed functions of EVs remains far from comprehensive, at least partly due to technical challenges in working with these small messengers. Here, we highlight areas of consensus as well as contentious issues in our understanding of the intracellular and intercellular journey of EVs: from biogenesis, release and dynamics in the extracellular space, to interaction with and uptake by recipient cells. We define knowledge gaps, identify key questions and challenges, and make recommendations on how to address these.