Paraspeckle-independent co-transcriptional regulation of nuclear microRNA biogenesis by SFPQ.

MicroRNAs (miRNAs) play crucial roles in physiological functions and disease, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, reveals its proximity to splicing factor proline- and glutamine (Q)-rich (SFPQ), a multifunctional RNA-binding protein (RBP) involved in forming paraspeckle nuclear condensates. SFPQ depletion impacts both primary and mature miRNA expression, while other paraspeckle proteins (PSPs) or the paraspeckle scaffolding RNA NEAT1 do not, indicating a paraspeckle-independent role. Comprehensive transcriptomic analyses show that SFPQ loss broadly affects RNAs and miRNA host gene (HG) expression, influencing both their transcription and the stability of their products. Notably, SFPQ protects the oncogenic miR-17∼92 polycistron from degradation by the nuclear exosome targeting (NEXT)-exosome complex and is tightly linked with its overexpression across a broad variety of cancers. Our findings reveal a dual role for SFPQ in regulating miRNA HG transcription and stability, as well as its significance in cancers.

The Bacterial Genomic Context of Highly Trimethoprim-Resistant DfrB Dihydrofolate Reductases Highlights an Emerging Threat to Public Health.

Type B dihydrofolate reductase (dfrb) genes were identified following the introduction of trimethoprim in the 1960s. Although they intrinsically confer resistance to trimethoprim (TMP) that is orders of magnitude greater than through other mechanisms, the distribution and prevalence of these short (237 bp) genes is unknown. Indeed, this knowledge has been hampered by systematic biases in search methodologies. Here, we investigate the genomic context of dfrbs to gain information on their current distribution in bacterial genomes. Upon searching publicly available databases, we identified 61 sequences containing dfrbs within an analyzable genomic context. The majority (70%) of those sequences also harbor virulence genes and 97% of the dfrbs are found near a mobile genetic element, representing a potential risk for antibiotic resistance genes. We further identified and confirmed the TMP-resistant phenotype of two new members of the family, dfrb10 and dfrb11. Dfrbs are found both in Betaproteobacteria and Gammaproteobacteria, a majority (59%) being in Pseudomonas aeruginosa. Previously labelled as strictly plasmid-borne, we found 69% of dfrbs in the chromosome of pathogenic bacteria. Our results demonstrate that the intrinsically TMP-resistant dfrbs are a potential emerging threat to public health and justify closer surveillance of these genes.