Biology subjects

Dou, S.

Publications and source records attributed to Dou, S..

5 recordsLinked to original sources

bioRxiv2025

The dynamics of ACR and DNA methylation impact asymmetric subgenome dominance in allotriploid Brassica species

Polyploidy plays a crucial role in the evolution and diversification of eukaryotes, often leading to structural and functional imbalances as multiple subgenomes merge. Numerous studies have demonstrated the phenomenon of asymmetric subgenome dominance in polyploid species. However, the subgenomic dominance resulting from interspecific hybridization with accessible chromatin regions (ACRs) and DNA methylation remains largely unexplored in allotriploids. We generated two allotriploid hybrids of Brassica species (ArAnCn) by crossing the allotetraploid Brassica napus (AnAnCnCn) with the diploid Brassica rapa (ArAr). Our results revealed that the An subgenome exhibits the highest levels of gene expression among the three subgenomes (Ar, An, and Cn) in F1 hybrids. However, the Cn subgenome that actually exerts dominance over An and Ar, as evidenced by the abundance of dominant triplet homologous genes. We found that the Cn subgenome contains a significantly higher density of ACRs than An and Ar subgenomes, and the expression levels of dominant triplet homologous genes are closely associated with the presence of ACRs in proximal and genic. Interestingly, variations in DNA methylation levels alone do not fully explain the expression advantages observed in F1 hybrids. We then discovered that reduced CHH methylation in F1 hybrids might be associated with decreased expression of BnaDCL3 and BnaDRM2 in the RNA-directed DNA methylation pathway. Furthermore, the mutants Bnadcl3CR and Bnardr2CR exhibited a selective preference for 24-nt small RNA and non-CG methylation in the An and Cn subgenomes. Overall, this study elucidates the relationship between ACRs, DNA methylation, and asymmetric subgenome dominance in resynthesis allotriploid species.

plant biology↗

bioRxiv2024

Upstream open reading frames buffer translational variability during Drosophila evolution and development

Protein abundance tends to be more evolutionarily conserved than mRNA levels both within and between species, yet the mechanisms underlying this phenomenon remain largely unknown. Upstream open reading frames (uORFs) are widespread cis-regulatory elements in eukaryotic genomes that regulate translation, but it remains unclear whether and how uORFs contribute to stabilizing protein levels. In this study, we performed ribosome translation simulations on mRNA to quantitatively assess the extent to which uORF translation influences the translational variability of downstream coding sequences (CDSs) across varying contexts. Our simulations revealed that uORF translation dampens CDS translational variability, with buffering capacity increasing in proportion to uORF efficiency, length, and number. We then compared the translatomes at different developmental stages of two Drosophila species, demonstrating that uORFs buffer mRNA translation fluctuations during both evolution and development. Experimentally, deleting a uORF in the bicoid (bcd) gene--a prominent example of translational buffering--resulted in extensive changes in gene expression and phenotypes in Drosophila melanogaster. Additionally, we observed uORF-mediated buffering between primates and within human populations. Together, our results reveal a novel regulatory mechanism by which uORFs stabilize gene translation during development and across evolutionary time.

evolutionary biology↗

bioRxiv2021

Ubiquitination and degradation of NF90 by Tim-3 inhibits antiviral innate immunity

Nuclear Factor 90 (NF90) is a novel virus sensor that serves to initiate antiviral innate immunity by triggering the stress granules (SGs) formation. However, the regulation of the NF90-SGs pathway remain largely unclear. We found that Tim-3, an immune checkpoint inhibitor, promotes the ubiquitination and degradation of NF90 and inhibits NF90-SGs mediated antiviral immunity. Vesicular Stomatitis Virus (VSV) infection induces the up-regulation and activation of Tim-3 in macrophages which in turn recruited the E3 ubiquitin ligase TRIM47 to the zinc finger domain of NF90 and initiated a proteasome-dependent degradation of the NF90 via K48-linked ubiquitination at Lys297. Targeted inactivation of the Tim-3 enhances the NF90 downstream SGs formation by selectively increasing the phosphorylation of PKR and eIF2a, the expression of SGs markers G3BP1 and TIA-1, and protected mice from lethal VSV challenge. These findings provide insights into the crosstalk between Tim-3 and other receptors in antiviral innate immunity and its related clinical significance.

immunology↗

bioRxiv2020

Evolutionary forces on A-to-I RNA editing revealed by sequencing individual honeybee drones

Social insects exhibit extensive phenotypic diversities among the genetically similar individuals, suggesting a role for the epigenetic regulations beyond the genome level. The ADAR-mediated adenosine-to-inosine (A-to-I) RNA editing, an evolutionarily conserved mechanism, facilitates adaptive evolution by expanding proteomic diversities. Here, we characterize the A-to-I RNA editome of honeybees (Apis mellifera), identifying 407 high-confidence A-to-I editing sites. Editing is most abundant in the heads, and shows signatures for positive selection. Editing behavior differs between foragers and nurses, suggesting a role for editing in caste differentiation. Although only five sites are conserved between bees and flies, an unexpectedly large number of genes exhibit editing in both species, albeit at different locations, including the nonsynonymous auto-editing of Adar. This convergent evolution, where the same target genes independently acquire recoding events in distant diverged clades, together with the signals of adaptation observed in honeybees alone, further supports the notion of recoding being adaptive.

evolutionary biology↗

bioRxiv2019

Mechanistic insights into NAD synthase NMNAT chaperoning phosphorylated Tau from pathological aggregation

Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimers disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD metabolism and Tau homeostasis in aging and neurodegeneration.

biochemistry↗