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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z adriana perezgrovas-saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is enriched in transcripts associated with psychiatri

关键词： 5-methylcytosine methylation Alzheimer’s disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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Effects of Tillage and Crop Residue Management on Maize Yields and Net Returns in the Central Mexican Highlands Under Drought Conditions

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Pedosphere 2014年第4期24卷 476-486页

作者： R.ROMERO-perezgrovas N.VERHULST D.DE LA ROSA V.HERNáNDEZ M.MAERTENS J.DECKERS B.GOVAERTS International Maize and Wheat Improvement Center(CIMMYT) P.O.Box 6-641Mexico D.F.06600(Mexico) Department of Earth and Environmental Sciences University of LeuvenCelestijnenlaan 200 ELeuven 3001(Belgium) Mathematics Research Center(CIMAT) Jalisco S/NValencianaGuanajuatoMexico CP 36240(Mexico)

In the subtropical highlands of Central Mexico,where the main crop is maize(Zea mays),the conventional practice(CP) involves tillage,monoculture and residue removal,leading to soil degradation and unsustainable use of natural resources and agricultural inputs.Conservation agriculture(CA) has been proposed as a viable alternative in the region,based on reduction in tillage,retention of adequate levels of crop residues and soil surface cover and use of crop rotation.This study began in 2009 when the highlands of Central Mexico suffered from a prolonged drought during vegetative maize growth in July-August,providing an opportunity for the on-farm comparison of CA with CP under severe drought conditions which 21 climate change models projected to become more frequent.Under dry conditions,CA resulted in higher yields and net returns per hectare as early as the first and second years after adoption by farmers.As an average of 27 plots under farmers' management in 2009,the maize yields were 26%higher under CA(6.3t ha^(-1)) than under CP(5.0 t ha^(-1)).2010 was close to a normal year in terms of rainfall so yields were higher than in 2009 for both practices;in addition,the yield difference between the practices was reduced to 19%(6.8 t ha^(-1) for CA vs.5.7 t ha^(-1) for CP).When all the 2009 and 2010 observations were analyzed in a modified stability analysis,CA had an overall positive effect of 3 838 Mexican Pesos ha^(-1)(320 $US ha^(-1)) on net return and 1.3 t ha^(-1) on yield.After only one to two years of adoption by farmers on their fields,CA had higher yields and net returns under dry conditions that were even drier than those predicted by the analyzed 21 climate change models under a climate change scenario,emission scenario A2.

关键词：玉米产量干旱条件耕作方式作物轮作墨西哥残留物管理气候变化模型

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