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Dou, S.

Publications and source records attributed to Dou, S..

2 recordsLinked to original sources

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

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