bims-micpro 2026-07-05 papers

Nat Biotechnol. 2026 Jun 30.

Prime editing for precise genome engineering and modulation of fungal metabolism.

Chunxiao Sun, Qiuyue Nie, Naomi Straub, Chris Keum, Yihui Shen, Xue Gao.

Prime editing has not been established in filamentous fungi, which are major ecological contributors and industrial hosts with vast biosynthetic capacity. Here we develop fPE7max, a prime editing platform optimized for fungi, which supports different edit types, including base substitutions and defined small insertions or deletions, with an average editing efficiency approaching 90%, across diverse genomic loci and species. fPE7max further enables larger insertions of up to 1 kb and deletions of up to 10 kb. We perturb upstream open reading frames in the pleiotropic regulator gene, laeA, to modulate metabolic output across multiple fungal species. Metabolomic profiling reveals activation of previously lowly biosynthetic pathways, leading to the identification of 18 metabolites, including 8, to our knowledge, previously unreported structures, 3 of which with cytotoxic activity. These results establish fPE7max as an efficient platform for genome engineering in filamentous fungi and show upstream open reading frame editing as a strategy for modulating endogenous regulatory networks and accessing the fungal chemical repertoire.

DOI: https://doi.org/10.1038/s41587-026-03202-4

Trends Biochem Sci. 2026 Jul 02. pii: S0968-0004(26)00180-5. [Epub ahead of print]

Peptideins: Navigating the gray zone of the proteome.

Giulia Pesce, Salvador Ventura.

Translated sequences are often treated as either genes or noise. A recent TransCODE Consortium study by Deutsch et al. introduces peptideins: endogenous proteins with evidence of synthesis but an unresolved biological status. This concept offers a cautious way to expand the human proteome while preserving the distinction between translation, molecular detection, and function.

Keywords: dark proteome; immunopeptidomics; microproteins; noncanonical ORFs; proteome annotation; ribosome profiling

DOI: https://doi.org/10.1016/j.tibs.2026.06.004

J Virol. 2026 Jun 24. e0010326

Sequence heterogeneity in pneumonia virus of mice reveals G gene-dependent modulation of virulence.

Akinbami R Adenugba, Patrick Bohn, Jiangyan Yu, Markus Fehrholz, Anke K Bergmann, Redmond P Smyth, Christine D Krempl.

Pneumonia virus of mice (PVM), the mouse homolog to respiratory syncytial virus (RSV), is increasingly used as a surrogate model to study pneumovirus pathogenesis in a more natural pathogen-host relationship. Two major strains of PVM, strain 15 and J3666, are currently used in laboratories, with preferences for either one or the other based on the well-documented isolation history of strain 15, or the suggested higher virulence of strain J3666. Using conventional and long-read sequencing, we found that the PVM strain J3666 represents two distinct virus populations, which are defined by the sequence and structure of the G and SH genes encoding the putative attachment and small hydrophobic proteins, in addition to further nucleotide polymorphisms. Specifically, a nucleotide polymorphism at position 65 in the G gene results in either an upstream open reading frame (uORF) preceding the main ORF in frame, or an extension of the major G ORF by 18 codons. The impact of the different forms of the J3666-G genes on PVM was examined by generating recombinant PVMs differing exclusively in the distinctive 5' portion of the respective G gene. This revealed that the population with an extended main G ORF was more virulent than the population with a G gene containing an uORF or the parental virus. The presence of a uORF was associated with decreased expression levels of G, whereas the virus with the extended G ORF appeared to express slightly increased levels of G, which suggests that expression levels of G may modulate virulence.
IMPORTANCE: The pneumonia virus of mice strain J3666 is considered a more virulent and more suitable model for severe lower respiratory tract infections. The organization of the gene for the attachment protein G is reported to contain a small upstream open reading frame (uORF) preceding the main G ORF in frame. The translated G protein is predicted to comprise 396 amino acids. We report that this virus strain may be a mixture of two different populations, each with differing virulence. The more virulent population encodes a G protein of potentially 414 amino acids instead of a small uORF. The usage of the first start codon in this G gene organization remains to be determined. Importantly, this organization of the G gene is in line with that of several newly identified pneumoviruses, i.e., canine and swine pneumoviruses. These viruses may comprise a distinct group within the Pneumoviridae family.

Keywords: attachment protein G gene; pneumonia virus of mice strain J3666; reverse genetics; sequence polymorphism; virulence

DOI: https://doi.org/10.1128/jvi.00103-26