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Kobayashi-Ishihara, M.

Publications and source records attributed to Kobayashi-Ishihara, M..

3 recordsLinked to original sources

Transposable elements as new players to decipher sex differences in Parkinson Disease

We present a novel integrative analysis of transposable elements (TEs) in 4 single cell RNA-seq (scRNA-seq) datasets of postmortem substantia nigra pars compacta samples of Parkinson Disease (PD) patients matched healthy controls, with the objective of building a cell-type specific trustworthy atlas of TEs that may clarify the role of TEs in sex differences in PD. We have used the soloTE tool to evaluate the TEs expression changes across all snRNA-seq studies identified in our previous systematic review, and then integrated the results using meta-analysis techniques. Finally, we evaluated the possible associations between TEs and protein coding genes by integrating our previous results in this matter with the information of TEs obtained, in order to propose the possible action mechanism by which some of the TEs contribute to PD.

bioinformatics↗

REFEE Shapes ZGA Through Post-Transcriptional Regulation of Repetitive RNAs in Mouse Embryos

During early mammalian embryonic development, repetitive elements such as transposons and duplicated genes are transcriptionally active and play key roles in embryogenesis. MERVL, an endogenous retrovirus, is essential for shaping the early transcriptome, particularly during the transition from totipotency to pluripotency. However, the function of many repetitive elements remains poorly understood. Here, we add a new repetitive player, REFEE, that regulates repetitive RNAs and contributes to totipotency regulation through post-transcriptional mechanisms. REFEE was initially identified as a paralogue of Alyref, a nucleocytoplasmic RNA exporter, transiently expressed during the 2-cell stage of mouse embryogenesis. REFEE preferentially binds and stabilizes MERVL RNA, promoting its export. REFEE knockdown embryos fail to complete zygotic genome activation (ZGA), accompanied by a significant reduction in MERVL RNA levels. REFEE primarily influences transcript levels of ZGA genes, upregulating or downregulating them in a manner correlated with their genomic proximity to MERVL. Proteomic analysis further revealed that REFEE knockdown also decreases protein levels of its RNA targets, indicating an additional layer of post-transcriptional regulation beyond RNA stability. Our findings identify REFEE as an essential post-transcriptional regulator of early embryonic development and highlight the functional interplay between repetitive elements in shaping the zygotic transcriptome.

developmental biology↗

Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1- infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal.

immunology↗