🧬 PubMed RNA Editing Daily Digest

A biofoundry integrates laboratory automation with Design-Build-Test-Learn (DBTL) workflows to accelerate strain development for sustainable manufacturing. Quantifying the economic efficiency of automated processes remains challenging. Here, we define the robot-assisted module (RAM) as a plug-and-play unit for constructing workflow and apply the Experiment Price Index (EPI), a standardized metric that combines time and cost per sample to evaluate and optimize synthetic biology workflows. Using EPI calculation and RAMs, we developed four workflows for strain development: guide (g)RNA cloning, genome editing, DNA assembly, and sample analysis. EPI identified workflow bottlenecks, elimination of redundancies, and assessment of techno-economic tradeoffs. We further extended the EPI framework on techno-economic assessment (TEA) by estimating return on investment (ROI) and payback periods for biofoundry operations at varying project scales. Our results demonstrate EPI for cost-effective experimental planning and scalable biofoundry deployment. Beyond strain engineering, EPI serves as a universal tool for evaluating automation efficiency across biotechnology.

Mitochondrial genomes (mt-genomes) of calcaronean sponges are among the most unusual in Metazoa. They are fragmented into multiple linear chromosomes (mt-chromosomes) and often rely on insertional mRNA editing to generate functional transcripts. These unusual features have precluded complete characterization of calcaronean mt-genomes using short-read sequencing technologies. Here, we assembled and analyzed the mt-genome of Sycon ciliatum (Fabricius, 1780) using HiFi PacBio data generated by the Aquatic Symbiosis Genomics Project. The mt-genome comprised several megabases of sequence distributed across thousands of chromosomes. While most protein-coding genes were preset in multiple copies, three typical animal mitochondrial protein-coding genes (atp8, nad4L and nad6) and multiple tRNA isotypes were not detected, and only short fragments of mt-rRNA genes were identified. We confirmed that mitochondrial mRNA editing in S. ciliatum occurred through single or double uridine insertions at 200+ sites, and that editing patterns were largely predictable from primary sequence motifs. Unexpectedly, editing sites varied among gene copies and were frequently disrupted by point mutations, leading to substantial changes in encoded amino acid sequences. Most mt-chromosomes were associated with repetitive elements that may function in genome maintenance and recombination. Together, our results reveal a distinctive mode of mt-genome evolution and function, shaped by extreme genome fragmentation, extensive gene duplication and pervasive RNA editing. This article is part of the theme issue 'Evolutionary genetics of mitochondria: on diverse and common evolutionary constraints across eukarya'.

Systemic lupus erythematosus (SLE) is a chronic, multi-organ autoimmune disease characterised by a highly heterogeneous presentation. Specific genetic variations predispose patients to the disease, and rare monogenic forms caused by single-gene variations have been identified in a small percentage of patients, often with early disease onset. In this study, we used exome sequencing in a large cohort of patient with juvenile-onset SLE to gain insight into the genetic basis of juvenile SLE (jSLE). Patients were selected if disease onset occurred before the age of 18. We performed exome sequencing on 263 individuals across 172 distinct families. The majority of cases were solo exomes (n = 118), while others included affected duos, trios, or multiplex families (n = 18 + 5 + 1), as well as classical trios with unaffected parents (n = 30). A molecular diagnosis consistent with the clinical presentation was established in 17 patients from unrelated families (10%). Among them, we identified pathogenic or likely pathogenic variants in genes previously associated with monogenic lupus, including a novel C1QA variant as well as other lupus-associated genes (COPA, ADAR, TLR7, IKZF3, RELA, PTPN11, SERPING1). Strikingly, exome sequencing also revealed variants in immunodeficiency-associated genes (IRAK4, USB1), autoinflammatory disorders (PSTPIP1) and unexpected candidates like ETV6, and MAN1B1 revealing previously unrecognised pathways in SLE development. Syndromic features and very early-onset (before the age of 5) were strongly associated with a higher diagnostic yield, reaching nearly 33% in these subgroups. This study expands our understanding of causes of lupus, highlighting its genetic heterogeneity. It also supports the systematic use of genetic testing in cases of juvenile lupus, especially those with very early onset or syndromic features, regardless of the clinical presentation. Given the range of unexpected molecular diagnoses identified in this study, pangenomic analysis such as exome or genome sequencing appears to be the most appropriate approach in these cases. This work was supported by: The Institut National de la Santé et de la Recherche Médicale (INSERM); Government grants managed by the Agence Nationale de la Recherche (ANR) as part of the "Investment for the Future" program: Institut Hospitalo-Universitaire Imagine (ANR-10-IAHU-01), Recherche Hospitalo-Universitaire (ANR-18-RHUS-0010); The Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH); The Fondation pour la Recherche Médicale (FRM: EQU202103012670, FDM202006011291); French and European grants managed by the ANR: ANR-14-CE14-0026 (Lumugène), ANR-21-CE17-0064 (SOCSIMMUNITY); The National Reference Center for Rheumatic, Autoimmune and Systemic Diseases in Children (RAISE).