Biology subjects

Bao, A.

Publications and source records attributed to Bao, A..

7 recordsLinked to original sources

bioRxiv2025

MANY PATHS TO DESTRUCTION: FAMILY-SPECIFIC TURNOVER AND STRESS RESPONSES FOR TRNA INTRONS

In organisms ranging from Archaea to humans, a subset of genes encoding tRNAs contain introns. Upon splicing, the tRNA exons are joined and the released free introns are rapidly degraded. Although tRNAs introns were previously considered to be "junk" sequences, we recently reported that free tRNA introns (fitRNAs) of S. cerevisiae serve as negative regulators of the cellular levels of mRNAs that bear long stretches of open reading frame sequence complementarity to tRNA introns. We also reported that 2 of the 10 families of tRNA introns, accumulate to elevated levels when cells suffer oxidative stress. The results led to the current investigations of the regulation of tRNA intron cellular levels. We document that tRNA intron turnover occurs by combinations of 5 RNA kinases, 5 to 3 and 3 to 5 exonucleases as well as by at least three endonucleases and, generally, the levels of each tRNA intron family are regulated by a unique combination of nucleases/kinases. Similarly, one family of excised intron can form circles whereas the other free tRNA intron families do not. Further, levels of individual tRNA introns differ in response to environmental conditions including type of media, stage in growth curves, and exposure to elevated temperature. Together, these findings highlight the many cellular pathways utilized to regulate tRNA intron levels and the specificity of these pathways for different tRNA families and varying cellular conditions. The results underscore the likely important roles of the newly discovered individual fitRNAs in regulation of cell biology and responses to environmental conditions.

molecular biology↗

bioRxiv2025

The China Brain Multi-omics Atlas Project (CBMAP)

The China Brain Multi-omics Atlas Project (CBMAP) aims to generate a comprehensive molecular reference map of over 1,000 human brains (Phase I), spanning a broad age range and multiple regions in China, to address the underrepresentation of East Asian populations in brain research. By integrating genome, epigenome, transcriptome, proteome (including multiple post-translational modifications), and metabolome data, CBMAP is set to provide a rich and invaluable resource for investigating the molecular underpinnings of aging-related brain phenotypes and neuropsychiatric disorders. Leveraging high-throughput omics data and advanced technologies, such as spatial transcriptomics, proteomics, and single-nucleus 3D chromatin structure analysis, this atlas will serve as a crucial resource for the brain science community, illuminating disease mechanisms and enhancing the utility of data from genome-wide association studies (GWAS). CBMAP is also poised to accelerate drug discovery and precision medicine for brain disorders.

neuroscience↗

bioRxiv2024

Transcriptional dissection of petty spurge (Euphorbia peplus L.) reproductive structures supports the Euphorbia cyathium as an inflorescence rather than a complete flower

The unique reproductive structure of Euphorbia species, the cyathium, is an inflorescence that resembles a single complete flower. This structure has not yet been investigated using transcriptomics at a genomic scale. Enabled by the petty spurge (Euphorbia peplus L.) genome and guided by the ABCDE model of floral development, we dissected petty spurge cyathia and carried out a transcriptomic analysis of the different organs. We also constructed gene phylogenies and performed dN/dS analysis on select floral genes. Unlike in model species in the Asteraceae, which also have pseudanthia (false flowers), we did not find evidence for lineage-specific duplications of E class genes in Euphorbia. Rather, our transcriptomic and genomic analyses indicate that SEP1 paralogs have distinct expression patterns within the cyathium. E. peplus filiform structures (sterile organs within the cyathium) show upregulation of B and E class genes and transcriptomic signatures of heterochromatin formation, consistent with some form of floral identity and potentially consistent with their being reduced flowers in an inflorescence. The gene CRABS CLAW (CRC), which is involved in nectary development in both arabidopsis and petunia, is not upregulated in E. peplus nectaries, indicating an alternative nectary development pathway in Euphorbia. Finally, Euphorbia homologs for the inflorescence/floral meristem genes UFO and LFY and the B class genes AP3 and PI have highly diverged sequences relative to other Euphorbiaceae species.

plant biology↗

bioRxiv2022

Chromosome-level genome assembly of Euphorbia peplus, a model system for plant latex, reveals that relative lack of Ty3 transposons contributed to its small genome size

Euphorbia peplus (petty spurge) is a small, fast-growing plant that is native to Eurasia and has become a naturalized weed in North America and Australia. E. peplus is not only medicinally valuable, serving as a source for the skin cancer drug ingenol mebutate, but also has great potential as a model for latex production owing to its small size, ease of manipulation in the laboratory, and rapid reproductive cycle. To help establish E. peplus as a new model, we generated a 267.2 Mb HiC-anchored PacBio HiFi nuclear genome assembly with an embryophyta BUSCO score of 98.5%, a genome annotation based on RNA-seq data from six tissues, and publicly accessible tools including a genome browser and an interactive organ-specific expression atlas. Chromosome number is highly variable across Euphorbia species. Using a comparative analysis of our newly sequenced E. peplus genome with other Euphorbiaceae genomes, we show that variation in Euphorbia chromosome number is likely due to fragmentation and rearrangement rather than aneuploidy. Moreover, we found that the E. peplus genome is relatively compact compared to related members of the genus in part due to restricted expansion of the Ty3 transposon family. Finally, we identify a large gene cluster that contains many previously identified enzymes in the putative ingenol mebutate biosynthesis pathway, along with additional gene candidates for this biosynthetic pathway. The genomic resources we have created for E. peplus will help advance research on latex production and ingenol mebutate biosynthesis in the commercially important Euphorbiaceae family. Significance statementEuphorbia is one of the five largest genera in the plant kingdom. Despite an impressive phenotypic and metabolic diversity in this genus, only one Euphorbia genome has been sequenced so far, restricting insights into Euphorbia biology. Euphorbia peplus has excellent potential as a model species due to its latex production, fast growth rate and production of the anticancer drug ingenol mebutate. Here, we present a chromosome-level E. peplus genome assembly and publicly accessible resources to support molecular research for this unique species and the broader genus. We also provide an explanation of one reason the genome is so small, and identify more candidate genes for the anticancer drug and related compounds.

plant biology↗

bioRxiv2021

Loss of Acta2 in cardiac fibroblasts does not affect myofibroblast differentiation or cardiac repair after myocardial infarction

In response to myocardial infarction (MI), quiescent cardiac fibroblasts differentiate into myofibroblasts mediating tissue repair in the infarcted area. One of the most widely accepted markers of myofibroblast differentiation is the expression of Acta2 which encodes smooth muscle alpha-actin (SMA) that is assembled into stress fibers. However, the requirement of Acta2 in the myofibroblast differentiation of cardiac fibroblasts and its role in post-MI cardiac repair were still not known. To answer these questions, we generated a tamoxifen-inducible cardiac fibroblast-specific Acta2 knockout mouse line. Surprisingly, mice that lacked Acta2 in cardiac fibroblasts had a normal survival rate after MI. Moreover, Acta2 deletion did not affect the function or overall histology of infarcted hearts. No difference was detected in the proliferation, migration, or contractility between WT cardiac fibroblasts and Acta2-null cardiac myofibroblasts. Additional analysis identified that Acta2-null cardiac myofibroblasts had a normal total filamentous actin level and total actin level. Acta2 deletion caused a unique compensatory increase in the transcription level of Actg2 and a possible increase in the protein abundance of cytoplasmic actin isoforms. In conclusion, the deletion of Acta2 does not prevent the myofibroblast differentiation of cardiac fibroblasts or affect the post-MI cardiac repair, and the increase in the expression of non-SMA actin isoforms and the functional redundancy between actin isoforms are likely able to compensate for the loss of Acta2 in cardiac myofibroblasts.

molecular biology↗

bioRxiv2021

Brain transcriptional regulatory architecture and schizophrenia etiology converge between East Asian and European ancestral populations

Understanding the genetic architecture of gene expression and splicing in human brain is critical to unlocking the mechanisms of complex neuropsychiatric disorders like schizophrenia (SCZ). Large-scale brain transcriptomic studies are based primarily on populations of European (EUR) ancestry. The uniformity of mono-racial resources may limit important insights into the disease etiology. Here, we characterized brain transcriptional regulatory architecture of East Asians (EAS; n=151), identifying 3,278 expression quantitative trait loci (eQTL) and 4,726 spliceQTL (sQTL). Comparing these to PsychENCODE/BrainGVEX confirmed our hypothesis that the transcriptional regulatory architecture in EAS and EUR brains align. Furthermore, distinctive allelic frequency and linkage disequilibrium impede QTL translation and gene-expression prediction accuracy. Integration of eQTL/sQTL with genome-wide association studies reveals common and novel SCZ risk genes. Pathway-based analyses showing shared SCZ biology point to synaptic and GTPase dysfunction as a prospective pathogenesis. This study elucidates the transcriptional landscape of the EAS brain and emphasizes an essential convergence between EAS and EUR populations.

genetics↗

bioRxiv2020

LocusFocus: A web-based colocalization tool for the annotation and functional follow-up of GWAS

Genome-wide association studies (GWAS) have primarily identified trait-associated loci in the non-coding genome. Colocalization analyses of SNP-level associations from GWAS with expression quantitative trait loci (eQTL) evidence enable the generation of hypotheses about responsible mechanism, genes and tissues of origin to guide functional characterization. Here, we present a web-based colocalization browsing and testing tool named LocusFocus (https://locusfocus.research.sickkids.ca). LocusFocus formally tests colocalization using our established Simple Sum method to identify the most relevant genes and tissues for a particular GWAS locus in the presence of high linkage disequilibrium and/or allelic heterogeneity. Full documentation and source code for LocusFocus are publicly available.

genomics↗