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At least 1,153 records · Page 64Linked to original sources

bioRxiv2026

Single-molecule nanopore-tweezers analysis of transcription elongation by intact and "stalk-less" yeast RNA polymerase II

Single-molecule picometer-resolution nanopore tweezers (SPRNT) enables monitoring of translocation of a nucleic-acid motor protein on a nucleic-acid track with sequence registration, sub-nucleotide spatial resolution, sub-millisecond temporal resolution, and the ability to apply forces that assist or oppose translocation. Recently, we used SPRNT to analyze the translocation of single molecules of Escherichia coli RNA polymerase relative to the DNA template strand during transcription elongation, and we directly detected sequence-dependent pausing and formation of a "half-translocated state" at the E. coli yrbL consensus pause element. Here, we apply SPRNT to analyze the translocation of single molecules of yeast RNA polymerase II (Pol II) relative to the DNA template strand during transcription elongation with single-nucleotide spatial resolution and millisecond-scale temporal resolution at biologically relevant, saturating substrate concentrations; we compare translocation by intact, 12-subunit Pol II to translocation by a 10-subunit Pol II sub-assembly lacking the dissociable Rpb4-Rpb7 Pol II "stalk"; and we assess possible pausing by intact Pol II and stalk-less Pol II at the E. coli yrbL consensus pause element. The results show that intact Pol II elongates more rapidly than stalk-less Pol II and show that neither intact Pol II nor stalk-less Pol II pauses at the E. coli yrbL consensus pause element. One-sentence summaryNanopore tweezers enable monitoring of translocation of RNA polymerase II relative to DNA in transcription elongation with single-nucleotide spatial resolution and millisecond-scale temporal resolution at biologically relevant, saturating substrate concentrations.

molecular biology↗

bioRxiv2026

Polystyrene microplastic exposure disrupts mitochondrial pathways and nuclear processes in primary intestinal epithelial cells

Microplastics are pervasive environmental pollutants that pose a growing concern for human health. Oral ingestion is a common route of human microplastic exposure, yet the proteomic response of the gut epithelium to microplastics remains unclear. This study aimed to investigate the cellular effects of pristine and artificially digested microplastic exposure in primary rat duodenal epithelial cells using untargeted proteomics. Cells were exposed to pristine or digested 0.5 um polystyrene microplastics at 10 or 100 ug/mL for 72 hours and were then analyzed by tandem liquid chromatography and mass spectrometry (LC-MS). Proteins that were both significantly different in intensity compared to controls, with a threshold change of 1.3 or greater, were considered to be differentially expressed. This criterion identified 41 differentially expressed proteins after 100 ug/mL pristine MP exposure, with 19 downregulated and 21 upregulated. Following exposure to 100 ug/mL digested MP, only 3 differentially expressed proteins were upregulated and 7 were down regulated, demonstrating the impact of microplastic physicochemistry. FGSEA pathway analysis revealed that 270 Reactome pathways were significantly altered following microplastic exposure in either condition at both concentrations. These pathways contributed to functional domains including protein synthesis, DNA replication, cell cycle control and aerobic respiration. Overall, microplastic exposure was associated with upregulated mitochondrial respiration, and downregulation of nuclear-related processes including DNA synthesis, transcription and cell proliferation. This study provides targets for future investigation (mitochondria and nucleus) and emphasizes the need to consider biological and environmental conditions for in vitro models of microplastic exposure.

molecular biology↗

bioRxiv2020

Orthogonal fluorescent chemogenetic reporters for multicolor imaging

Fluorescence microscopy is an indispensable tool in biological research, allowing sub-second and sub-micrometer mapping of molecules or processes inside living cells. Moreover, using spectrally separated fluorophores, one can observe multiple targets simultaneously, leading to a deeper understanding of the dynamic molecular interplays that regulate cell function and fate. Chemogenetic systems, which combine a protein tag and a synthetic fluorophore, provide certain advantages over fluorescent proteins since there is no requirement for chromophore maturation. However, the fluorophore promiscuity of chemogenetic systems renders two-color applications challenging. Here, we present the engineering of a set of spectrally orthogonal fluorogen activating tags based on the Fluorescence Activating and absorption Shifting Tag (FAST), that are compatible with two-color, live cell imaging. The resulting tags, greenFAST and redFAST, demonstrate orthogonality not only in their fluorogen recognition capabilities, but also in their one- and two-photon absorption profiles. A two-color cell cycle sensor based on greenFAST and redFAST is capable of detecting very short, early cell cycles in zebrafish development which had previously been difficult to image. Furthermore, this pair of orthogonal tags can be developed into split complementation systems that are capable of detecting multiple protein-protein interactions by live cell fluorescence microscopy.

molecular biology↗

bioRxiv2020

Structures of the Human LONP1 Protease Reveal Regulatory Steps Involved in Protease Activation

The human mitochondrial AAA+ protein LONP1 is a critical quality control protease involved in regulating diverse aspects of mitochondrial biology including proteostasis, electron transport chain activity, and mitochondrial transcription. As such, genetic or aging-associated imbalances in LONP1 activity are implicated in the pathologic mitochondrial dysfunction associated with numerous human diseases. Despite this importance, the molecular basis for LONP1-dependent proteolytic activity remains poorly defined. Here, we solved cryo-electron microscopy structures of human LONP1 to reveal the molecular mechanism of substrate proteolysis. We show that, like bacterial Lon, human LONP1 adopts both an open and closed spiral staircase orientation dictated by the presence of substrate and nucleotide. However, unlike bacterial Lon, human LONP1 contains a second spiral staircase within its ATPase domain that engages substrate to increase interactions with the translocating peptide as it transits into the proteolytic chamber for proteolysis. Further, we show that substrate-bound LONP1 includes a second level of regulation at the proteolytic active site, wherein autoinhibition of the active site is only relieved by the presence of a peptide substrate. Ultimately, our results define a structural basis for human LONP1 proteolytic activation and activity, establishing a molecular framework to understand the critical importance of this protease for mitochondrial regulation in health and disease.

molecular biology↗

bioRxiv2016

High-resolution interrogation of functional elements in the noncoding genome

The noncoding genome plays a major role in gene regulation and disease yet we lack tools for rapid identification and manipulation of noncoding elements. Here, we develop a large-scale CRISPR screen employing ~18,000 sgRNAs targeting >700 kb of noncoding sequence in an unbiased manner surrounding three genes (NF1, NF2, and CUL3) involved in resistance to the BRAF inhibitor vemurafenib in the BRAF-mutant melanoma cell line A375. We identify specific noncoding locations near genes that modulate drug resistance when mutated. These sites have predictive hallmarks of noncoding function, such as physical interaction with gene promoters, evolutionary conservation and tissue-specific chromatin accessibility. At a subset of identified elements at the CUL3 locus, we show that engineered mutations lead to a loss of gene expression associated with changes in transcription factor occupancy and in long-range and local epigenetic environments, implicating these sites in gene regulation and chemotherapeutic resistance. This demonstration of an unbiased mutagenesis screen across large noncoding regions expands the potential of pooled CRISPR screens for fundamental genomic discovery and for elucidating biologically relevant mechanisms of gene regulation.

Molecular Biology↗

bioRxiv2021

Epoxidized graphene grid for high-throughput high-resolution cryoEM structural analysis

Many specimens suffer from low particle density and/or preferred orientation in cryoEM specimen grid preparation, making data collection and structure determination time consuming. We developed an epoxidized graphene grid (EG-grid) that effectively immobilizes protein particles by applying an oxidation reaction using photoactivated ClO2* and further chemical modification. The particle density and orientation distribution are both dramatically improved, having enabled us to reconstruct the density map of GroEL and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), at 1.99 and 2.16 [A] resolution from only 504 and 241 micrographs, respectively. A low concentration sample solution of 0.1 mg ml-1 was sufficient to reconstruct a 3.10 [A] resolution density map of SARS-CoV-2 spike protein from 1,163 micrographs. The density maps of V1-ATPase, {beta}-galactosidase, and apoferritin were also reconstructed at 3.03, 1.81, and 1.29 [A] resolution, respectively. These results indicate that the EG-grid will be a powerful tool for high-throughput cryoEM data collection to accelerate high-resolution structural analysis of biological macromolecules.

molecular biology↗

bioRxiv2024

Synphilin-1 as a modulator of aSyn assembly

Alpha-synuclein (aSyn) is an intrinsically disordered protein that undergoes phase-separation and is associated with several neurodegenerative conditions. However, the function and the pathological role of aSyn are still elusive. Here, we modeled different types of aSyn assemblies in living cells, and developed a model that reports on gel and solid-like inclusions based on the coexpression of aSyn and synphilin-1 (Sph1). We identified striking morphological differences between aSyn-aSyn and Sph1-aSyn assemblies, characterized by distinct antibody recognition patterns, resistance to Proteinase K treatment, and protein mobilities. Importantly, we showed that the interaction between Sph1-aSyn can be manipulated, altering inclusion size and number. Sph1-aSyn interactions were central for inclusion formation and localization, and that inclusions include lysosomes and AP-1 vesicles, consistent with previous studies in human brain tissue. In total, we provide novel insight into the biology of protein aggregation, shedding light on potential therapeutic strategies that extend beyond conventional targets. Deciphering the role of Sph1 and other aSyn-interacting proteins on aSyn biology and pathobiology will be essential for treating synucleinopathies.

molecular biology↗

bioRxiv2025

Creation and Validation of a Proteome-Wide Yeast Library for Protein Detection and Analysis

A significant challenge in cell biology is to uncover the function of uncharacterized proteins. Surprisingly a quarter of the proteome is still poorly understood even in the most well studied model organisms. Systematic methodologies, including the use of tagged protein collections, have emerged as a powerful approach to address this gap. Despite the availability of proteome- wide collections featuring various fused proteins, the impact of tag size on protein function highlighted the need for using minimally disruptive tags for functional genomic studies. To rise to this challenge, we have created a proteome-wide collection of yeast strains in which proteins are N-terminally tagged with the Hemagglutinin (HA) epitope. The library leverages the compact size of the HA tag to minimize drawbacks associated with larger tags while enabling efficient functional analysis. We showcase the potential uses of our library for systematically evaluating protein size, abundance and localization using an in vivo labeling approach. Our characterization underscores the potential utility of a proteome-wide HA-tagged library in revealing novel aspects of cell biology, providing an additional powerful tool for functional genomics.

molecular biology↗

bioRxiv2025

Reducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATAC

Large-scale scATAC-seq experiments are challenging because of their costs, lengthy protocols, and confounding batch effects. Several sample multiplexing technologies aim to address these challenges, but do not remove batch effects introduced when performing transposition reactions in parallel. We demonstrate that sample-to-sample variability in nuclei-to-Tn5 ratios is a major cause of batch effects and develop MULTI-ATAC, a multiplexing method that pools samples prior to transposition, as a solution. MULTI-ATAC provides high accuracy in sample classification and doublet detection while eliminating batch effects associated with variable nucleus-to-Tn5 ratio. We illustrate the power of MULTI-ATAC by performing a 96-plex multiomic drug assay targeting epigenetic remodelers in a model of primary immune cell activation, uncovering tens of thousands of drug-responsive chromatin regions, cell-type specific effects, and potent differences between matched inhibitors and degraders. MULTI-ATAC therefore enables batch-free and scalable scATAC-seq workflows, providing deeper insights into complex biological processes and potential therapeutic targets.

molecular biology↗

bioRxiv2025

A safer fluorescent in situ hybridization protocol for cryosections

Fluorescent in situ hybridization (FISH) enables highly sensitive, high-resolution detection of gene transcripts. Moreover, by employing multiple probes, this technique allows for multiplexed, simultaneous detection of distinct gene expression patterns spatiotemporally, making it a valuable spatial transcriptomics approach. Owing to these advantages, FISH techniques are rapidly being adopted across diverse areas of basic biology. However, conventional protocols often rely on volatile, toxic reagents such as formalin or methanol, posing potential health risks to researchers. Here, we present a safer protocol that replaces these chemicals with low-toxicity alternatives, without compromising the high detection sensitivity of FISH. We validated this protocol using both in situ hybridization chain reaction (HCR) and signal amplification by exchange reaction (SABER)-FISH in frozen sections of various model organisms, including mouse (Mus musculus), amphibians (Xenopus laevis and Pleurodeles waltl), and medaka (Oryzias latipes). Our results demonstrate successful multiplexed detection of morphogenetic and cell-type marker genes in these model animals using this safer protocol. The protocol has the additional advantage of requiring no proteolytic enzyme treatment, thus preserving tissue integrity. Furthermore, we show that this protocol is fully compatible with EGFP immunostaining, allowing for the simultaneous detection of mRNAs and reporter proteins in transgenic animals. This protocol retains the benefits of highly sensitive, multiplexed, and multimodal detection afforded by integrating in situ HCR and SABER-FISH with immunohistochemistry, while providing a safer option for researchers, thereby offering a valuable tool for basic biology.

molecular biology↗

bioRxiv2025

Breaking Bad: Exploring & Complementing the Effects of the DNASE1L3 p.Arg206Cys Variant on Cell-Free DNA from an Isogenic Cell Line Model

DNASE1L3 is a key endonuclease, essential for proper fragmentation and clearance of cell-free DNA (cfDNA). The p.R206C common variant impairs DNASE1L3 secretion and activity, causing aberrant cfDNA fragmentation and therefore affecting liquid biopsy-based screening and diagnostics. Existing studies on DNASE1L3 relied on resource-intensive murine models or plasmid-based overexpression, which do not accurately represent native expression. To address this, we developed an isogenic HEK293T cell line model by using CRISPR Prime Editing for endogenous expression of DNASE1L3R206C. We analyzed the cfDNA composition directly from conditioned culture medium and found that fragment size distributions in mutant cells mimics the hypofragmented profiles previously observed in plasma samples from p.R206C carriers. We also showed that in vitro treatment of hypofragmented cfDNA with recombinant wildtype DNASE1L3 could enrich for mononucleosomal fragments, with fragment end-motifs characteristic of DNASE1L3 cleavage activity. This could open avenues for DNASE1L3 as a candidate pre-treatment agent to improve the accuracy and efficiency of cfDNA sequencing-based diagnostics in hypofragmented liquid biopsies. These findings demonstrate that our isogenic cell line model provides a controlled system to study cfDNA fragmentation biology and DNASE1L3 function.

molecular biology↗

bioRxiv2025

Expression of four mitochondrial tRNAs from only two loci

Transfer RNAs (tRNAs) are among the few genes retained in animal mitochondrial genomes after more than a billion years of gene loss. These ancient bacterial vestiges are often structurally aberrant and less stable than their bacterial or cytosolic tRNA counterparts. In some lineages, mitochondrial tRNAs (mt-tRNAs) have become so truncated that the loss of one or both arms has expanded our understanding of what constitutes a functional tRNA. Here, we report another radical departure from canonical tRNA gene architecture: two overlapping tRNAs produced from opposite strands of the same locus. These mirror tRNA pairs eliminate the need to retain separate loci for all tRNA genes, as a single locus can produce tRNAs to decode two different amino acids. We show that these mirror tRNAs are aminoacylated and demonstrate their presence in mitoribosomes. Furthermore, mirror tRNAs display strand-specific patterns of nucleotide modification and RNA editing, reflecting specific post-transcriptional maturation that depends on transcriptional orientation. To our knowledge, this demonstration of functional, bidirectional tRNA expression is a first for any genome or organism and reveals an unexpected strategy by which mitochondrial genomes maintain a complete set of tRNAs in the face of unrelenting gene loss. The discovery of mirror tRNAs has broad implications for the evolution of tRNA-interacting enzymes, mitochondrial biology, and even the origins of the protein synthesis machinery itself.

molecular biology↗

bioRxiv2019

CreLite: An Optogenetically Controlled Cre/loxP System Using Red Light

Precise manipulation of gene expression with temporal and spatial control is essential for functional studies and the determination of cell lineage relationships in complex biological systems. The Cre-loxP system is commonly used for gene manipulation at desired times and places. However, specificity is dependent on the availability of tissue- or cell-specific regulatory elements used in combination with Cre or CreER (tamoxifen-inducible). Here we present CreLite, an optogenetically-controlled Cre system using red light in developing zebrafish embryos. Cre activity is disabled by splitting Cre and fusing the inactive halves with the Arabidopsis thaliana red light-inducible binding partners, PhyB and PIF6. In addition, PhyB-PIF6 binding requires phycocyanobilin (PCB), providing an additional layer of control. Upon exposure to red light (660 nm) illumination, the PhyB-CreC and PIF6-CreN fusion proteins come together in the presence of PCB to restore Cre activity. Red-light exposure of transgenic zebrafish embryos harboring a Cre-dependent multi-color fluorescent protein reporter (ubi:zebrabow) injected with CreLite mRNAs and PCB, resulted in Cre activity as measured by the generation of multi-spectral cell labeling in various tissues, including heart, skeletal muscle and epithelium. We show that CreLite can be used for gene manipulations in whole embryos or small groups of cells at different stages of development. CreLite provides a novel optogenetic tool for precise temporal and spatial control of gene expression in zebrafish embryos that may also be useful in cell culture, ex vivo organ culture, and other animal models for developmental biology studies.

molecular biology↗

bioRxiv2026

Validated backbone assignments for natural-abundance 1H,15N spectra of commercial hen egg white lysozyme and example applications thereof

Although backbone 1H and 15N assignments for hen egg white lysozyme (HEWL) have been reported in the literature and several related entries are available in the BMRB, these resources differ in sequence, experimental conditions, and the nuclei represented. In particular, there is no BMRB entry with an explicit set of 1H,15N backbone assignments applicable to spectra that can now be collected at natural 15N abundance on concentrated samples of commercial HEWL as shown by Bruker and reproduced here using a 800 MHz magnet with a cryoprobe. Therefore, here I make available the backbone 1H,15N chemical shifts of commercial (Sigma) HEWL at pH 3.8 and 308 K parsed from previous papers and checked against 1H,1H NOESY, 1H,1H TOCSY and 1H,15N correlation spectra of HSQC and SOFAST-HMQC types, acquired on a 3 mM sample at natural 15N abundance. I also provide backbone 1H,15N assignments transferred to pH 6 and 308 K via a pH titration, closer to physiological conditions as used by others. I discuss details about sample preparation and spectra acquisition, including the measurement times involved, and possible reasons for a few residues lacking assignments. The usefulness of these assignments and of detecting 1H,15N correlations at natural abundance are proven by (i) application to a titration with a small molecule, (ii) studies of hydration and dynamics via Het-SOFAST-HMQC experiments, and ultimately (iii) by their utilization in published papers even if without attribution. I deliver ready-to-use assignments as text-format Sparky files, and make selected spectra available on the PDB Manipulation Suite's WebNMR app for straightforward visualization online, useful also for swift educational demonstrations. Overall, I expect the data and methods presented here will be of use in protein biophysics and structural biology research and education, by enabling the interpretation of modern NMR-based studies on inexpensive samples of this widely studied protein.

molecular biology↗

bioRxiv2023

Structural basis for differential p19 targeting by IL-23 biologics

BackgroundIL-23 is central to the pathogenesis of psoriasis, and is structurally comprised of p19 and p40 subunits. "Targeted" IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab differ mechanistically from ustekinumab because they bind p19, whereas ustekinumab binds p40; however, a knowledge gap exists regarding the structural composition of their epitopes and how these molecular properties relate to their clinical efficacy. ObjectivesTo characterize and differentiate the structural epitopes of the IL-23 inhibitors risankizumab, guselkumab, tildrakinumab, and ustekinumab, and correlate their molecular characteristics with clinical response in plaque psoriasis therapy. MethodsWe utilized epitope data derived from hydrogen-deuterium exchange studies for risankizumab, tildrakizumab, and guselkumab, and crystallographic data for ustekinumab to map drug epitope locations, hydrophobicity, and surface charge onto the IL-23 molecular surface (Protein Data Bank ID Code 3D87) using UCSF Chimera. PDBePISA was used to calculate solvent accessible surface area (SASA). Epitope composition was determined by classifying residues as acidic, basic, polar, or hydrophobic and calculating their contribution to epitope SASA. Linear regression and analysis of variance was performed. ResultsAll the p19-specific inhibitor epitopes differ in location and size, with risankizumab and guselkumab having large epitope surface areas (SA), and tildrakizumab and ustekinumab having smaller SA. The tildrakizumab epitope was mostly hydrophobic (56%), while guselkumab, risankizumab, and ustekinumab epitopes displayed >50% non-hydrophobic residues. Risankizumab and ustekinumab exhibited acidic surface charges, while tildrakizumab and guselkumab were net neutral. Each inhibitor binds an epitope with a unique size and composition, and with mostly distinct locations except for a 10-residue overlap region that lies outside of the IL-23 receptor epitope. We observed a strong correlation between epitope SA and PASI-90 rates (R2 = 0.9969, p = 0.0016), as well as between epitope SA and KD (R2 = 0.9772, p = 0.0115). In contrast, we found that total epitope hydrophobicity, polarity, and charge content do not correlate with clinical efficacy. ConclusionsStructural analysis of IL-23 inhibitor epitopes reveals strong association between epitope SA and early drug efficacy in plaque psoriasis therapy, exemplifying how molecular data can explain clinical observations, inform future innovation, and help clinicians in specific drug selection for patients.

molecular biology↗

bioRxiv2017

Identification of Pathways Associated with Chemosensitivity through Network Embedding

Basal gene expression levels have been shown to be predictive of cellular response to cytotoxic treatments. However, such analyses do not fully reveal complex genotype-phenotype relationships, which are partly encoded in highly interconnected molecular networks. Biological pathways provide a complementary way of understanding drug response variation among individuals. In this study, we integrate chemosensitivity data from a recent pharmacogenomics study with basal gene expression data from the CCLE project and prior knowledge of molecular networks to identify specific pathways mediating chemical response. We first develop a computational method called PACER, which ranks pathways for enrichment in a given set of genes using a novel network embedding method. It examines known relationships among genes as encoded in a molecular network along with gene memberships of all pathways to determine a vector representation of each gene and pathway in the same low-dimensional vector space. The relevance of a pathway to the given gene set is then captured by the similarity between the pathway vector and gene vectors. To apply this approach to chemosensitivity data, we identify genes with basal expression levels in a panel of cell lines that are correlated with cytotoxic response to a compound, and then rank pathways for relevance to these response-correlated genes using PACER. Extensive evaluation of this approach on benchmarks constructed from databases of compound target genes, compound chemical structure, as well as large collections of drug response signatures demonstrates its advantages in identifying compound-pathway associations, compared to existing statistical methods of pathway enrichment analysis. The associations identified by PACER can serve as testable hypotheses about chemosensitivity pathways and help further study the mechanism of action of specific cytotoxic drugs. More broadly, PACER represents a novel technique of identifying enriched properties of any gene set of interest while also taking into account networks of known gene-gene relationships and interactions.

pharmacology and toxicology↗

bioRxiv2021

Stop Bickering! Reconciling Signaling Pathway Databases with Network Topologies

A major goal of molecular systems biology is to understand the coordinated function of genes or proteins in response to cellular signals and to understand these dynamics in the context of disease. Signaling pathway databases such as KEGG, NetPath, NCI-PID, and Panther describe the molecular interactions involved in different cellular responses. While the same pathway may be present in different databases, prior work has shown that the particular proteins and interactions differ across database annotations. However, to our knowledge no one has attempted to quantify their structural differences. It is important to characterize artifacts or other biases within pathway databases, which can provide a more informed interpretation for downstream analyses. In this work, we consider signaling pathways as graphs and we use topological measures to study their structure. We find that topological characterization using graphlets (small, connected subgraphs) distinguishes signaling pathways from appropriate null models of interaction networks. Next, we quantify topological similarity across pathway databases. Our analysis reveals that the pathways harbor database-specific characteristics implying that even though these databases describe the same pathways, they tend to be systematically different from one another. We show that pathway-specific topology can be uncovered after accounting for database-specific structure. This work present the first step towards elucidating common pathway structure beyond their specific database annotations.

systems biology↗

bioRxiv2020

Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator

Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activation in vivo and identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interaction in vitro was unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Structural modeling showed that ADs interact with Med15 without shape complementarity ("fuzzy" binding). ADs shared no sequence motifs, but mutagenesis revealed biochemical and structural constraints. Finally, a neural network trained on AD sequences accurately predicted ADs in human proteins and in other yeast proteins, including chromosomal proteins and chromatin remodeling complexes. These findings solve the longstanding enigma of AD structure and function and provide a rationale for their role in biology.

molecular biology↗