Origins of neuronal diversity: Although the main task of a neuroprogenitor is to produce more cells, it may not always produce the same cells. Some progenitors produce different daughter neurons as an embryo develops. Concurrently, these daughter neurons are also transitioning through states toward maturation. Telley et al. used single-cell RNA sequencing to survey the transcriptional identity of cells early in mouse brain development. As a neuroprogenitor transitioned to new states, it produced daughter neurons that reflect those new states. The neuron's own postmitotic differentiation program is apparently overlaid onto these parentally supplied programs, driving emergence of specialized neuronal cell types in the neocortex. Science , this issue p. eaav2522
Tracking neuronal transcriptional programs: Early in brain development, cortical neurons are born near the ventricles, then migrate to their functional destinations. Telley et al. used a fluorescent labeling technique to see what transcripts characterize these earliest stages of neural development. Waves of transcriptional programs are initiated, then passed by as the neuron progresses from proliferative to migratory and finally to connectivity phases. Science , this issue p. 1443
Bacteria depend on efficient RNA turnover, both during homeostasis and when rapidly altering gene expression in response to changes. Nevertheless, remarkably few details are known about the rate-limiting steps in targeting and decay of RNA. The membrane-anchored endoribonuclease RNase Y is a virulence factor in Gram-positive pathogens. We have obtained a global picture of Staphylococcus aureus RNase Y sequence specificity using RNA-seq and the novel transcriptome-wide EMOTE method. Ninety-nine endoribonucleolytic sites produced in vivo were precisely mapped, notably inside six out of seven genes whose half-lives increase the most in an RNase Y deletion mutant, and additionally in three separate transcripts encoding degradation ribonucleases, including RNase Y itself, suggesting a regulatory network. We show that RNase Y is required to initiate the major degradation pathway of about a hundred transcripts that are inaccessible to other ribonucleases, but is prevented from promiscuous activity by membrane confinement and sequence preference for guanosines. Ribonucleic acids (RNA) are key intermediates between the heritable genome and the expression of proteins. Thus the level of a specific RNA determines the capability of the cell to produce the corresponding protein. Bacteria maintain a very high turnover (high production but also high decay-rate) of RNA molecules, to ensure that they can, at any time, change the protein production program in response to outside stimuli. However, all types of RNA molecules do not have the same half-life, some last for tens of minutes whereas most only last for seconds. Here we examine how endoribonuclease Y (RNase Y), one of the enzymes that cleave RNA into smaller fragments, chooses its targets from the pool of cellular RNA. We show that RNase Y prefers to cleave RNA at a specific ribonucleotide sequence, thus keeping the RNA degradation to the correct level, not too fast and not too slow. RNase Y is anchored to the inside of the cell envelope, and we furthermore show that releasing RNase Y into the interior of the cell results in poor growth, but is at the same time able to compensate for the loss of CshA, another factor in the RNA decay machinery.