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Start Over Author "Giorgia Modenini" Topic retrotransposons
2 results on '"Giorgia Modenini"'

1. The coevolution between APOBEC3 and retrotransposons in primates

Author

Giorgia Modenini, Paolo Abondio, and Alessio Boattini

Subjects
APOBEC3, Retrotransposons, Primates, Homo, Brain diseases, Evolutionary arms race, Genetics, QH426-470
Abstract

Abstract Retrotransposons are genetic elements with the ability to replicate in the genome using reverse transcriptase: they have been associated with the development of different biological structures, such as the Central Nervous System (CNS), and their high mutagenic potential has been linked to various diseases, including cancer and neurological disorders. Throughout evolution and over time, Primates and Homo had to cope with infections from viruses and bacteria, and also with endogenous retroelements. Therefore, host genomes have evolved numerous methods to counteract the activity of endogenous and exogenous pathogens, and the APOBEC3 family of mutators is a prime example of a defensive mechanism in this context. In most Primates, there are seven members of the APOBEC3 family of deaminase proteins: among their functions, there is the ability to inhibit the mobilization of retrotransposons and the functionality of viruses. The evolution of the APOBEC3 proteins found in Primates is correlated with the expansion of two major families of retrotransposons, i.e. ERV and LINE-1. In this review, we will discuss how the rapid expansion of the APOBEC3 family is linked to the evolution of retrotransposons, highlighting the strong evolutionary arms race that characterized the history of APOBEC3s and endogenous retroelements in Primates. Moreover, the possible role of this relationship will be assessed in the context of embryonic development and brain-associated diseases.

Published
2022
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2. A retrotransposon storm marks clinical phenoconversion to late-onset Alzheimer's disease

Author

Fabio Macciardi, Maria Giulia Bacalini, Ricardo Miramontes, Alessio Boattini, Cristian Taccioli, Giorgia Modenini, Rond Malhas, Laura Anderlucci, Yuriy Gusev, Thomas J. Gross, Robert M. Padilla, Massimo S. Fiandaca, Elizabeth Head, Guia Guffanti, Howard J. Federoff, Mark Mapstone, Macciardi, Fabio, Giulia Bacalini, Maria, Miramontes, Ricardo, Boattini, Alessio, Taccioli, Cristian, Modenini, Giorgia, Malhas, Rond, Anderlucci, Laura, Gusev, Yuriy, Gross, Thomas J, Padilla, Robert M, Fiandaca, Massimo S, Head, Elizabeth, Guffanti, Guia, Federoff, Howard J, and Mapstone, Mark

Subjects
Aging, Retroelements, Blood biomarker, Neurodegenerative, Alzheimer's Disease, Blood biomarkers, Transposable element, Alzheimer Disease, Machine learning, Acquired Cognitive Impairment, Genetics, Humans, 2.1 Biological and endogenous factors, Retrotransposon, Aetiology, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer disease, Gene expression, Retrotransposons, Transposable elements, Biomarker, Brain Disorders, Neurological, RNA, Dementia, Geriatrics and Gerontology, Biomarkers, Human
Abstract

Recent reports have suggested that the reactivation of otherwise transcriptionally silent transposable elements (TEs) might induce brain degeneration, either by dysregulating the expression of genes and pathways implicated in cognitive decline and dementia or through the induction of immune-mediated neuroinflammation resulting in the elimination of neural and glial cells. In the work we present here, we test the hypothesis that differentially expressed TEs in blood could be used as biomarkers of cognitive decline and development of AD. To this aim, we used a sample of aging subjects (age > 70) that developed late-onset Alzheimer’s disease (LOAD) over a relatively short period of time (12–48 months), for which blood was available before and after their phenoconversion, and a group of cognitive stable subjects as controls. We applied our developed and validated customized pipeline that allows the identification, characterization, and quantification of the differentially expressed (DE) TEs before and after the onset of manifest LOAD, through analyses of RNA-Seq data. We compared the level of DE TEs within more than 600,000 TE-mapping RNA transcripts from 25 individuals, whose specimens we obtained before and after their phenotypic conversion (phenoconversion) to LOAD, and discovered that 1790 TE transcripts showed significant expression differences between these two timepoints (logFC ± 1.5, logCMP > 5.3, nominal p value phenoconversion, this TE storm features significant increases in DE transcripts of LINEs, LTRs, and SVAs, while those for SINEs are significantly depleted. These dysregulations end with signs of manifest LOAD. This set of highly DE transcripts generates a TE transcriptional profile that accurately discriminates the before and after phenoconversion states of these subjects. Our findings suggest that a storm of DE TEs occurs before phenoconversion from normal cognition to manifest LOAD in risk individuals compared to controls, and may provide useful blood-based biomarkers for heralding such a clinical transition, also suggesting that TEs can indeed participate in the complex process of neurodegeneration.

Published
2022

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