No abstract

m6A is a prevalent internal modification in mRNAs and has been linked to the diverse effects on mRNA fate. To explore the landscape and evolution of human m6A, we generated 27 m6A methylomes across major adult tissues. These data reveal dynamic m6A methylation across tissue types, uncover both broadly or tissue-specifically methylated sites, and identify an unexpected enrichment of m6A methylation at non-canonical cleavage sites. A comparison of fetal and adult m6A methylomes reveals that m6A preferentially occupies CDS regions in fetal tissues. Moreover, the m6A sub-motifs vary between fetal and adult tissues or across tissue types. From the evolutionary perspective, we uncover that the selection pressure on m6A sites varies and depends on their genic locations. Unexpectedly, we found that ∼40% of the 3′UTR m6A sites are under negative selection, which is higher than the evolutionary constraint on miRNA binding sites, and much higher than that on A-to-I RNA modification. Moreover, the recently gained m6A sites in human populations are clearly under positive selection and associated with traits or diseases. Our work provides a resource of human m6A profile for future studies of m6A functions, and suggests a role of m6A modification in human evolutionary adaptation and disease susceptibility.

Adenosine-to-inosine (A-to-I) RNA editing regulates miRNA biogenesis and function. To date, fewer than 160 miRNA editing sites have been identified. Here, we present a quantitative atlas of miRNA A-to-I editing through the profiling of 201 pri-miRNA samples and 4694 mature miRNA samples in human, mouse, and We identified 4162 sites present in ∼80% of the pri-miRNAs and 574 sites in mature miRNAs. miRNA editing is prevalent in many tissue types in human. However, high-level editing is mostly found in neuronal tissues in mouse and Interestingly, the edited miRNAs in neuronal and non-neuronal tissues in human gain two distinct sets of new targets, which are significantly associated with cognitive and organ developmental functions, respectively. Furthermore, we reveal that miRNA editing profoundly affects asymmetric strand selection. Altogether, these data provide insight into the impact of RNA editing on miRNA biology and suggest that miRNA editing has recently gained non-neuronal functions in human.

We applied proteomics technologies to analyze the cerebrospinal fluid of patients with schizophrenia. Such an analysis can result in the identification of proteins, which may play a role in the disease progress and thus lead to the discovery of clues of the etiology of schizophrenia. Cerebrospinal fluid from patients and controls was analyzed by two-dimensional gels and the proteins were identified by matrix-assisted laser desorption ionization mass spectrometry (MS) in the MS and MS/MS mode. 54 different gene products were identified, which were mainly plasma proteins. The level of apolipoprotein A-IV was significantly decreased in the schizophrenic patients compared to that in the controls. Little is known about the function of this apolipoprotein in the central nervous system. The levels of certain other proteins, like haptoglobin, fibrinogen, complement component 3, and Gc-globulin, were altered in the disease group as well, however, the changes did not reach a statistical significance.

ObjectiveTo study the efficacy of grip strength (GS) as a predictor of cognitive function in a large, nationwide sample of Chinese participants aged 45 years and above.MethodsWe used data from three waves (W1, W2, and W3) fielded by the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was tested biennially and calculated using two categories: episodic memory and mental intactness. Demographics, health behaviors, and medical conditions were considered potential confounders. Using multivariate linear regression models (MLRMs), we examined the association between baseline GS (measure in W1) and cognitive function in W3. Using a generalized estimating equation (GEE), we examined baseline GS as a predictor of cognitive function change.ResultsTotal 9,333 individuals (53.2% women), with a mean baseline episodic memory score of 6.5, mean baseline mental intactness score of 7.2, and aged over 45 years (mean age = 58.6), were selected. The mean follow-up time was 4.0 years (range: 3.3–5.0 years). Using MLRMs and comparing the lowest GS score with the highest baseline GS score, we observed a significant correlation with a higher global cognitive function in both women (β = 1.061, p < 0.001) and men (β = 1.233, p < 0.001). After adjusting baseline global cognition, the highest GS level was still statistically significant in both women (β = 0.543, p < 0.05) and men (β = 0.742, p < 0.001). GEE suggested that the participants in the highest GS quartile had better cognitive performance over time in both women (β = 0.116, p = 0.030) and men (β = 0.143, p = 0.008) than those in the lowest quartile.ConclusionHigher baseline level of GS was significantly related to better cognitive function and slowed the rate of its decline. Thus, it is an independent predictor of better cognitive status in middle-aged and elderly Chinese.