Findings reveal an evolutionary shift from gene-specific transcriptional regulation toward a regime where genome architecture becomes a regulator of gene expression.
Abstract
Transcriptional regulation of protein-coding genes is a hallmark of eukaryotic gene expression. Yet, a group of parasitic protists, trypanosomatids, appear to lack this capability. Here, we analyzed genomic, nascent transcriptomic, RNA polymerase occupancy and gene organization data to reconstruct the evolutionary origin and biological consequences of their unusual regulatory strategy. Across 59 Discoba protists, we show stepwise evolutionary erosion of conventional transcription regulation components in trypanosomatida lineage, including gene consolidation into polycistronic transcription units (PTUs), shortening of intra-PTU non-coding regions, and depletion of transcription factors and their enriched DNA-binding motifs. This transition was associated with near-constitutive expression of most genes, indicating broad loss of conditional gene expression. However, trypanosomatids retain some differential regulation at the PTU level, with >70% PTUs featuring significantly different nascent transcription than their neighbors or resident chromosomes. Moreover, gene expression is not uniform within PTUs: nascent transcription, translation efficiency, and protein abundance progressively decline with distance from the transcription start site. Consistent with this architecture-encoded regulatory logic, co-complex subunits and co-pathway enzymes preferentially occupy adjacent positions within PTUs despite each PTU’s overall functional heterogeneity. These findings reveal an evolutionary shift from gene-specific transcriptional regulation toward a regime where genome architecture becomes a regulator of gene expression.
The findings of this study reveal that transcriptional events in these unicellular parasites are more complex than believed thus far: not all transcriptional events are constitutive, polycistronic transcription is not the only mode of transcription, and cis-acting sequence elements regulate at least some transcriptional events in these parasites.
A. Singh, Vishal Dashora, Arushi Khanna et al.· Microbiology spectrum· 0 citations
These findings reconstruct the evolutionary emergence of the DGF-1 architecture from pre-existing structural modules and provide a framework for one of the largest and most enigmatic gene families in trypanosomatids.
Mathias J. Mangino, Juan Manuel Trinidad-Barnech, A. Parodi-Talice et al.· bioRxiv· 0 citations
Helicoverpa armigera is one of the most destructive lepidopteran pests worldwide owing to its remarkable polyphagy, long-distance migration, and rapid adaptation to insecticides. Here, we present a chromosome-level genome assembly of H. armigera generated from a field-collected individual in southwestern China, providing a valuable resource for future population genomic and pangenome studies. Developmental transcriptome analyses of first-instar larvae, fifth-instar larvae, and adults identified 6817, 3519, and 5518 differentially expressed genes, respectively, including 797 shared among all developmental transitions. Functional enrichment and co-expression network analyses revealed extensive transcriptional reprogramming, characterized by coordinated regulation of glycolysis, the tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation, indicating dynamic metabolic remodeling during development. Genome-wide analysis identified 77 heat shock protein (HSP) genes belonging to six subfamilies. These genes were unevenly distributed across chromosomes, with HSP20 members exhibiting extensive tandem duplication. Expression profiling revealed pronounced stage specificity, suggesting progressive remodeling of molecular chaperone networks during development. Early larvae primarily relied on HSP40/HSP60/HSP70 and HSP10/HSP60 chaperone systems; fifth-instar larvae exhibited HSP20-centered proteostasis; and adults predominantly expressed HSP40 together with multiple HSP70 members, accompanied by enrichment of stress response and metamorphosis-related functions. This study provides new insights into developmental transcriptional regulation, metabolic remodeling, and stage-specific specialization of molecular chaperone networks in H. armigera, establishing a foundation for future studies of stress adaptation, population genomic variation, and developmental mechanisms.
Cheng-Ren Ouyang, Wen-Qi Yang, Ying-Fen Yang et al.· Genomics· 0 citations
Trichomonas vaginalis is the causative agent of trichomoniasis, a common sexually transmitted infection among women of reproductive and peri-menopausal age. The parasite has an unusually large genome, rich in complex repeats, including a vast repertoire of transposable elements and multi-copy gene families. Since very few T. vaginalis genes have introns, gene expression is usually straightforward, with ribosomal translational machinery proceeding from a start codon to the next in-frame stop codon of an unspliced poly(A)denylated mRNA. However, our previous studies raised the possibility of T. vaginalis gene expression involving stop codon readthrough (SCR), where transcription through in-frame stop codons produces longer-than-predicted mRNAs that translate to fully functional proteins. Here, we leverage long-read RNA-seq and new chromosome-scale assemblies of two T. vaginalis strains and two avian sister species to investigate and characterize ∼1,400 long, mature mRNAs that contain more than one predicted protein-coding gene transcribed from what we call ‘RT genes’, composites of adjacent predicted genes. We first identify RT genes in a second T. vaginalis strain and in close relatives T. vaginalis-like and T. stableri, indicating that this phenomenon is conserved among Trichomonas species and strains. Second, we find transcripts of RT genes to be more abundant by many orders of magnitude than monocistronic genes. Third, we found the distance between predicted genes within RT genes to be significantly shorter than between adjacent independent predicted genes. Fourth, functional annotation revealed that RT genes encode at least 50 distinct protein functions, suggesting that this unusual transcriptional mechanism has a role in an array of biological processes in Trichomonas. Our results from two Trichomonas species suggest that SCR is an important mechanism controlling gene expression and the diversity of protein function in this parasite.
Francisco Callejas-Hernández, Mari Shiratori, Madison Pleas et al.· bioRxiv· 0 citations
Transposable elements (TEs) are pervasive genomic components that propagate via self-encoded factors, yet the nature, regulation, and function of these factors remain largely unresolved. Here, we integrated extensive long- and short-read transcriptome data, regulatory network analyses, deep proteomics, and structural predictions to construct a comprehensive atlas of TE products in Arabidopsis. We show that TE expression is embedded within host regulatory circuits, with DNA methylation and transcription factors jointly shaping TE transcriptional activity. Proteomic analyses confirm the production of over a hundred of high-confidence TE-encoded proteins, and structure-guided analyses of the transcript-informed TE proteome predict previously uncharacterized structural folds, multimerization capacity, and host protein interaction potential. Structural alignments further uncover cryptic homologies between TE-encoded proteins and host factors, including cases of domestications and co-options. Together, our study reveals the functional integration of TEs into cellular pathways and underscores the role of TEs as active drivers of genome function and innovation. Transposable elements (TEs) are pervasive in host genomes and propagate via self-encoded factors. Here, the authors show that control of TE expression and propagation is deeply embedded within host regulatory circuits.
Carles Borredá, Pol Vendrell-Mir, Basile Leduque et al.· Nature Communications· 1 citation
Viruses encode diverse regulatory elements, but their breadth and mechanisms remain poorly defined. To address this gap, we performed massively parallel reporter assays spanning ∼200,000 genomic segments from 297 vertebrate-infecting viral genera. We identified numerous viral elements that enhance RNA stability and translation through TENT4-mediated mixed tailing, distributed across 19 genera and grouped into six distinct subclasses, indicating extensive convergent evolution. We also found diverse TENT4-independent elements acting through alternative pathways. One such element, Pt1 from Potamipivirus, stabilizes linear mRNA to levels comparable to circular RNA, suggesting its potential for RNA therapeutics. Pt1 directly recruits canonical poly(A) polymerases (PAPγ/α)-previously thought to function exclusively in transcription-coupled nuclear pre-mRNA processing-to drive cytoplasmic polyadenylation. Together, these findings chart the rich landscape of viral regulation, extend the scope of poly(A)-tail biology, and establish the virome as a valuable source for uncovering host RNA regulatory mechanisms.
Jenny J Seo, Che-Min Lee, Dongbin Lim et al.· Cell· 1 citation
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