Protonation-dependent sequencing of 5-formylcytidine in RNA.

Chemical modification of cytidine in non-coding RNAs plays a key role in regulating translation and disease. However, the distribution and dynamics of many of these modifications remains unknown due to a lack of sensitive site-specific sequencing technologies. Here we report a protonation-dependent sequencing reaction for detection of 5-formylcytidine (5fC) and 5-carboxycytidine (5caC) in RNA. First, we evaluate how protonation combined with electron withdrawing substituents alters the molecular orbital energies and reduction of modified cytidine nucleosides, highlighting 5fC and 5caC as reactive species. Next, we apply this reaction to detect these modifications in synthetic oligonucleotides as well as endogenous human tRNA. Finally, we demonstrate the utility of our method to characterize a patient-derived model of 5fC-deficiency, where it enables facile monitoring of both pathogenic loss and exogenous rescue of NSUN3-dependent 5fC within the wobble base of human mitochondrial tRNAMet . These studies showcase the ability of protonation to enhance the reactivity and sensitive detection of 5fC in RNA, and provide a molecular foundation for applying optimized sequencing reactions to better understand the role of oxidized RNA cytidine nucleobases in disease

Supernova siblings and their parent galaxies in the Zwicky Transient Facility Bright Transient Survey

International audienceSupernova (SN) siblings – two or more SNe in the same parent galaxy – are useful tools for exploring progenitor stellar populations as well as properties of the host galaxies such as distance, star-formation rate, dust extinction, and metallicity. Since the average SN rate for a Milky Way-type galaxy is just one per century, a large imaging survey is required to discover an appreciable sample of SN siblings. From the wide-field Zwicky Transient Facility (ZTF) Bright Transient Survey (which aims for spectroscopic completeness for all transients which peak brighter than r < 18.5 mag) we present 10 SN siblings in five parent galaxies. For each of these families, we analyse the SN’s location within the host and its underlying stellar population, finding agreement with expectations that SNe from more massive progenitors are found nearer to their host core and in regions of more active star formation. We also present an analysis of the relative rates of core collapse and thermonuclear SN siblings, finding a significantly lower ratio than past SN sibling samples due to the unbiased nature of the ZTF