🧬 PubMed RNA Editing Daily Digest

A-to-I RNA editing, catalyzed by the adenosine deaminase acting on RNA (ADAR) enzymes, is a posttranscriptional process that modifies RNA sequences and diversifies the transcriptome. ADARs bind to double-stranded RNA (dsRNA) and their specificity and efficiency are affected by the structural properties of these substructures. In most cases, the dsRNA structure arises from homology between two segments of the same RNA molecule that fold into RNA stem structures. Another possible source of dsRNA is cotranscription of sense and antisense strands of the same genomic region. Binding of these complementary, naturally occurring, antisense transcripts (NATs) results in a perfect RNA duplex, which may be targeted by ADARs. To explore the scope of ADAR editing of NAT-derived dsRNA, we examined editing levels at genome locations where both strands are transcribed. Our findings indicate that editing is rare in regions for which both strands cotranscribe. Moreover, even when RNA editing does occur in NAT regions, it is typically associated with secondary structures on a single strand, suggesting that editing depends on intramolecular structures rather than binding of NATs.

The insufficient contribution of human cells is a key obstacle to interspecies chimera. In this issue of Developmental Cell, He et al. harnessed the RNA collateral cleavage activity of Cas13 to diminish the competitive advantage of host cells, increasing integration ratio of human cells to 1% in host mice.

Robust biocontainment is essential for the safe use of engineered microbes, but existing strategies suffer from genetic instability and/or laborious construction. Here, we present ATTACH, a kill switch that associates toxin-antitoxin with CRISPR-Cas to harness engineered microbes. Our approach employs a CRISPR-repressed toxin-antitoxin (CreTA) module to make microbes addicted to the type I-F Cas effector proteins, and places both the Cas3 nuclease and the chromosome-targeting guide RNA under inducible promoters, thereby improving the genetic stability and stringency of the CRISPR-based suicidal program. Additionally, we have developed a single-plasmid, antibiotic-independent ATTACH device, which shows robust, stringent containment of a microbial chassis in murine gut, and negligible impacts on culture growth or lycopene production during batch fermentation. Our data highlight the potential of CreTA to stabilize CRISPR-based kill switches, advancing their development into more portable and reliable biocontainment tools for engineered microbes.

Research has indicated a connection between pyroptosis and psoriasis, yet the specific genes involved remain largely unidentified. This study employed Mendelian randomization (MR) to evaluate the potential causal impact of both pyroptosis-related genes and DNA methylation signatures on psoriasis risk. Pyroptosis-related genes were sourced from the GeneCards database. We integrated quantitative trait locus (QTL) data, including expression (eQTLs), DNA methylation (mQTLs), and protein expression (pQTLs). The GCST90014456 database provided genome-wide association study (GWAS) data for psoriasis, using the FinnGen and UKB cohorts for validation. Summary data-based Mendelian randomization (SMR) analysis assessed interactions between these genes and psoriasis, while colocalization analysis identified shared causal genetic variants. SMR analysis identified 82 methylation sites, 18 gene, and 2 protein were associated with psoriasis risk. Multi-omics integration highlighted ADAR, which increased methylation at cg27530370 was associated with decreased ADAR expression (OR = 0.505, 95% CI [0.421-0.607]). Additionally, DNMT3B, PROM2, and KIF11 were the intersection genes of mQTL and eQTL analysis, and were validated by the UKB cohort in eQTL analysis, and NFKB1 was validated by the UKB cohort in pQTL analysis. This multi-omics analysis reveals that pyroptosis-related genes, particularly ADAR, DNMT3B, PROM2, KIF11, and NFKB1, may be involved in psoriasis development, providing important insights into its molecular mechanisms and potential therapeutic targets.