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CRISPR base editors can induce single-base-pair changes in the genome, although they are often inefficient. A study now shows that fusion of the DNA-binding domain of RAD51 to base editors enhances both the efficiency and the targeting range of optimized enzymes. These ‘hyper-editors’ offer effective tools for disease modeling and gene therapy.
Pluripotent cells generate all types of cells in the body and have largely been classified dichotomously into two types: naïve and primed. Arguing against a binary classification system, a study now discovers a unique transition state between naïve and primed pluripotency and describes the signals that control this transition.
Active transport along microtubules by molecular motors is a crucial cellular process that is disrupted in human diseases. Single-molecule studies from three independent groups reveal a new molecular mechanism for how cells control the activity of the complex microtubule motor cytoplasmic dynein via the neurodevelopmental protein LIS1.
Post-translational histone modifications are important regulators of nuclear reprogramming. A study now reveals that histone lysine demethylase KDM4A-mediated H3K9me3 demethylation in mammalian oocytes is essential for zygotic genome activation and preimplantation development.
Groth and colleagues discuss recent advances in chromatin replication and maintenance across mitotic division, with emphasis on replication-coupled chromatin assembly and chromatin maturation post-replication.
YAP and TAZ, paralogous mammalian genes, act as the key transcriptional effectors of the Hippo pathway. Two recent reports show that both YAP and TAZ form liquid–liquid phase-separated bodies that promote gene transcription by engaging in super-enhancers.
Piwi proteins are aberrantly induced in human tumours, but their function in cancer has been poorly understood. A study now shows that in the absence of piRNA loading, human PIWIL1 promotes pancreatic cancer metastasis by acting as a co-activator of the anaphase-promoting complex/cyclosome (APC/C) to degrade the cell-adhesion protein Pinin.
The lack of endogenous reporter lines is a bottleneck in the study of subcellular dynamics in human adult stem cell (ASC)-derived organoids. An approach using CRISPR–Cas9-mediated homology-independent organoid transgenesis (CRISPR–HOT) in ASC-derived organoids now narrows the gap between basic research and translational studies in human organoids.
Misfolded proteins in the endoplasmic reticulum (ER) are returned to the cytosol and destroyed by a process known as ER-associated degradation (ERAD). Hrd1 has been implicated as the channel that mediates the transport of ERAD substrates to the cytosol. A study demonstrates that Hrd1 is gated by autoubiquitination and a soluble ERAD substrate.
Gene editing holds promise for the treatment of cancers that are driven by well-characterised molecular alterations. A study now provides a proof of concept for the feasibility of in vivo gene editing to correct TERT mutations in glioblastoma, providing a platform for the direct manipulation of genetic alterations to reduce tumour growth.
Understanding the metabolic rewiring of pancreatic ductal adenocarcinoma is an emerging strategy for identifying cancer-associated liabilities and improving treatment. A new study now elucidates the function of the transaminase BCAT2 in the early stages of tumor development, providing insights that could stimulate novel therapeutic strategies.
The ribosome decodes messenger RNAs and constructs proteins based on the genetic blueprint. Ribosomes also associate with non-coding RNAs, such as PIWI-interacting RNA (piRNA) precursors, during the meiotic pachytene stage. Intriguingly, the ribosome mediates pachytene piRNA biogenesis by guiding endonucleolytic cleavage of piRNA precursors.
RNA-targeting CRISPR. In this Perspective, Smargon, Shi and Yeo discuss the rapid development of the RNA-targeting CRISPR–Cas engineering system and highlight how this can be leveraged to further understand RNA biology.
A mechanism of secretory autophagy explains aspects of the packaging of proteins and RNA into extracellular vesicles and paves the way to a better understanding of their biological roles and medical applications.
The molecular clock regulates the rhythmic transcription of myriad genes, leading to a circadian pattern of expression of the encoded proteins. A study demonstrates circadian regulation of expression of components of the protein secretory pathway, providing a mechanism to generate circadian patterns of secreted protein expression.
