PHD3 controls energy homeostasis and exercise capacity.
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This manuscript was submitted in error therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Genome sequence of Tricholoma matsutake was revealed as the one of the large fungal genomes published up to date at 189.0 Mbp with 15,305 predicted genes. The unusual size of this fungal genome contained frequent colonization of transposable elements (TEs) occupying more than half of the entire genome. We identified that 702 genes were surrounded by TEs and 83.2% of those genes were never transcribed at any development stage. This observation corroborated that the insertion of transposable elements alters the transcription of the genes neighboring TEs.\n\nRepeat-induced point mutation such as C to T hypermutation with a bias over CpG dinucleotides was also recognized in this genome, representing a typical defense mechanism against TEs during evolution. Many transcription factor genes were activated in both primordia and fruiting body, which indicates that many regulatory processes are shared during developmental stages. Small secreted protein genes (<300 aa) were dominantly transcribed in hyphae, where symbiotic interactions occur with hosts. Comparative analysis with 37 Agaricomycetes genomes revealed that IstB-like domain (PF01695) was conserved in taxonomically diverse mycorrhizal genomes, where the T. matsutake genome contained four copies of this domain. Three of the IstB-like genes were overexpressed in hyphae. In the CAZyme analysis, reduced CAZyme genes were found as other ectomycorrhizal genomes including a lot of loss of glycoside hydrolase genes. Also, auxiliary activity genes were dominantly transcribed in primordia. The T. matsutake genome sequence provides insight into the large genome size and clues to understand unusual fungal genome expansion.
The investigational drugs E7820, indisulam and tasisulam (aryl-sulfonamides) promote the degradation of the splicing factor RBM39 in a proteasome-dependent mechanism. While the activity critically depends on the Cullin RING ligase substrate receptor DCAF15, the molecular details remain elusive. Here we present the cryo-EM structure of the DDB1-DCAF15-DDA1 core ligase complex bound to RBM39 and E7820 at 4.4 [A] resolution, together with crystal structures of engineered subcomplexes. We show that DCAF15 adopts a novel fold stabilized by DDA1, and that extensive protein-protein contacts between the ligase and substrate mitigate low affinity interactions between aryl-sulfonamides and DCAF15. Our data demonstrates how aryl-sulfonamides neo-functionalize a shallow, non-conserved pocket on DCAF15 to selectively bind and degrade RBM39 and the closely related splicing factor RBM23 without the requirement for a high affinity ligand, which has broad implications for the de novo discovery of molecular glue degraders.
Substantial N2O emission results from activated sludge nitrogen removal processes. The importance of N2O-reducers possessing NosZ-type N2O reductases have been recognized as the only N2O sink in situ key to determination of the net N2O emissions; however, reliable quantification methods for nosZ genes and transcripts have yet to be developed. Here, nosZ genes and transcripts in activated sludge tank microbiomes were analyzed with the group-specific qPCR assays designed de novo combining culture-based and computational approach. A sewage sample was enriched in a batch reactor fed continuous stream of N2 containing 20-10,000 ppmv N2O, where 14 genera of potential N2O-reducers were identified. All available amino acid sequences of NosZ affiliated to these taxa were grouped into five subgroups (two clade I and three clade II groups), and primer/probe sets exclusively and comprehensively targeting the subgroups were designed and validated with in silico PCR. Four distinct activated sludge samples from three different wastewater treatment plants in Korea were analyzed with the qPCR assays and the results were validated by comparison with the shotgun metagenome analysis results. With the validated qPCR assays, the nosZ genes and transcripts of six additional activated sludge samples were analyzed and the results of the analyses clearly indicated the dominance of two clade II nosZ subgroups (Flavobacterium-like and Dechloromonas-like) among both nosZ gene and transcript pools.