Biology subjects

Miller, J. T.

Publications and source records attributed to Miller, J. T..

6 recordsLinked to original sources

bioRxiv2026

40S Ribosome Remodeling Triggers 18S rRNA U-tailing and DIS3L2-dependent Decay

Eliminating defective ribosomes through quality control is essential for accurate protein synthesis. However, the mechanisms that commit ribosomal subunits to decay remain poorly defined. Here, we identify a tandem mechanism in which ubiquitin-mediated ribosome remodeling and 18S rRNA uridylation lead to 40S ribosomal subunit decay. Specifically, we use an in vitro reconstitution system to show that the atypical kinase RIOK3 displaces the ribosomal protein eS26 from 40S subunits, exposing the 3 end of 18S rRNA. Nanopore direct RNA sequencing and motif analyses reveal that this remodeling event promotes oligo-uridylation, generating uridylated 18S rRNA decay intermediates. We further show that this uridylated 18S rRNA is selectively degraded by the 3-5 exoribonuclease DIS3L2. Moreover, DIS3L2-mediated exoribonucleolytic cleavage triggers endoribonucleolytic decay of the 18S rRNA, amplifying turnover. Together, our findings define a stepwise mechanism in which ribosome remodeling and RNA tailing commit defective 40S subunits to elimination, establishing a mechanistic framework for ribosome surveillance in mammalian cells.

molecular biology↗

bioRxiv2026

A large phylogenetic tree for euphyllophytes

PremiseMolecular datasets for estimating phylogenetic trees increasingly include more species and gene regions. Often trees are constructed using backbone phylogenies, subtrees, and other techniques to address the challenges of large dataset size. Currently, there is no established approach to integrate these rapidly expanding datasets. MethodsWe generated a phylogenetic tree (and 1,000 bootstrap trees) with divergence times that span euphyllophytes. To do this, we integrated taxonomically broad dated backbone phylogenies with species-level trees generated from phylogenetic analysis of individual clades. Datasets for species-level trees were assembled using PyPHLAWD. ResultsThe resulting dated phylogenetic tree includes: 121,641 angiosperm species; 1,026 gymnosperms; and 5,603 ferns. This is the largest euphyllophyte phylogenetic tree constructed to date. Topological uncertainty spikes at the start of the Cretaceous and gradually increases during the Cenozoic. Uncertainty in age estimates gradually increases in the Cenozoic but increases dramatically in the most recent 5 Myrs. DiscussionThis dated phylogenetic framework can underpin evolutionary studies spanning euphyllophytes, and enable the integration of insights from the recent to the distant past. Our approach also enables the tree to be easily updated in the future to reflect future increases in data availability, and systematic and taxonomic advances within specific clades.

plant biology↗

bioRxiv2024

The integrated stress response regulates 18S nonfunctional rRNA decay in mammals

18S nonfunctional rRNA decay (NRD) detects and eliminates translationally nonfunctional 18S rRNA. While this process is critical for ribosome quality control, the mechanisms underlying nonfunctional 18S rRNA turnover remain elusive. NRD was originally identified and has exclusively been studied in Saccharomyces cerevisiae. Here, we show that 18S NRD is conserved in mammals. Using genome-wide CRISPR genetic interaction screens, we find that mammalian NRD acts through the integrated stress response (ISR) via GCN2 and ribosomal protein ubiquitination by RNF10. Selective ribosome profiling reveals nonfunctional 18S rRNA induces translational arrest at start sites. Indeed, biochemical analyses demonstrate that ISR activation limits translation initiation and attenuates collisions between scanning 43S preinitiation complexes and nonfunctional 80S ribosomes arrested at start sites. Overall, the ISR promotes nonfunctional 18S rRNA and 40S ribosomal protein turnover by RNF10-mediated ubiquitination. These findings establish a dynamic feedback mechanism by which the GCN2-RNF10 axis surveils ribosome functionality at translation initiation.

molecular biology↗

bioRxiv2023

Independently evolved pollution resistance in four killifish populations is largely explained by few variants of large effect

The genetic architecture of phenotypic traits can affect the mode and tempo of trait evolution. Human-altered environments can impose strong natural selection, where successful evolutionary adaptation requires swift and large phenotypic shifts. In these scenarios, theory predicts the influence of few adaptive variants of large effect, but empirical studies that have revealed the genetic architecture of rapidly evolved phenotypes are rare, especially for populations inhabiting polluted environments. Fundulus killifish have repeatedly evolved adaptive resistance to extreme pollution in urban estuaries. Prior studies, including genome scans for signatures of natural selection, have revealed some of the genes and pathways important for evolved pollution resistance, and provide context for the genotype-phenotype association studies reported here. We created multiple quantitative trait locus (QTL) mapping families using progenitors from four different resistant populations, and genetically mapped variation in sensitivity (developmental perturbations) following embryonic exposure to a model toxicant PCB-126. We found that a few large-effect QTL loci accounted for resistance to PCB- mediated developmental toxicity. QTLs harbored candidate genes that govern the regulation of aryl hydrocarbon receptor (AHR) signaling, where some (but not all) of these QTL loci were shared across all populations, and some (but not all) of these loci showed signatures of recent natural selection in the corresponding wild population. Some strong candidate genes for PCB resistance inferred from genome scans in wild populations were identified as QTL, but some key candidate genes were not. We conclude that rapidly evolved resistance to the developmental defects normally caused by PCB-126 is governed by few genes of large effect. However, other aspects of resistance beyond developmental phenotypes may be governed by additional loci, such that comprehensive resistance to PCB-126, and to the mixtures of chemicals that distinguish urban estuaries more broadly, may be more genetically complex.

evolutionary biology↗

bioRxiv2022

Precipitation is the main axis of tropical phylogenetic turnover across space and time

Early natural historians - Compte de Buffon, von Humboldt and De Candolle - established ecology and geography as two principal axes determining the distribution of groups of organisms, laying the foundations for biogeography over the subsequent 200 years, yet the relative importance of these two axes remains unresolved. Leveraging phylogenomic and global species distribution data for Mimosoid legumes, an pantropical plant clade of 3,400 species, we show that the water availability gradient from deserts to rainforests dictates turnover of lineages within continents across the tropics. We demonstrate that 95% of speciation occurs within a precipitation niche, showing profound phylogenetic niche conservatism, and that lineage turnover boundaries coincide with isohyets of precipitation. We reveal similar patterns on different continents, implying that evolution and dispersal follow universal processes.

evolutionary biology↗

bioRxiv2020

A chromosome level genome of Astyanax mexicanus surface fish for comparing population-specific genetic differences contributing to trait evolution.

Identifying the genetic factors that underlie complex traits is central to understanding the mechanistic underpinnings of evolution. In nature, adaptation to severe environmental change, such as encountered following colonization of caves, has dramatically altered genomes of species over varied time spans. Genomic sequencing approaches have identified mutations associated with troglomorphic trait evolution, but the functional impacts of these mutations remain poorly understood. The Mexican Tetra, Astyanax mexicanus, is abundant in the surface waters of northeastern Mexico, and also inhabits at least 30 different caves in the region. Cave-dwelling A. mexicanus morphs are well adapted to subterranean life and many populations appear to have evolved troglomorphic traits independently, while the surface-dwelling populations can be used as a proxy for the ancestral form. Here we present a high-resolution, chromosome-level surface fish genome, enabling the first genome-wide comparison between surface fish and cavefish populations. Using this resource, we performed quantitative trait locus (QTL) mapping analyses for pigmentation and eye size and found new candidate genes for eye loss such as dusp26. We used CRISPR gene editing in A. mexicanus to confirm the essential role of a gene within an eye size QTL, rx3, in eye formation. We also generated the first genome-wide evaluation of deletion variability that includes an analysis of the impact on protein-coding genes across cavefish populations to gain insight into this potential source of cave adaptation. The new surface fish genome reference now provides a more complete resource for comparative, functional, developmental and genetic studies of drastic trait differences within a species.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genomics↗