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Phase II for N6-methyladenosine RNA modification-based biodosimeters for absorbed ionizing radiation dose estimation

ABSTRACT: Phase II for N6-methyladenosine RNA modification-based biodosimeters for absorbed ionizing radiation dose estimation

PROVIDER: PRJNA935403 | ENA |

REPOSITORIES: ENA

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Phase I for N6-methyladenosine RNA modification-based biodosimeters for absorbed ionizing radiation dose estimation

Project description:Phase I for N6-methyladenosine RNA modification-based biodosimeters for absorbed ionizing radiation dose estimation

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RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation.

Project description:Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.

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N6-Methyladenosine methylation profile in rat H9C2 cardiomyocytes under the hypoxic stress

Project description:Hypoxia as a crucial pathogenesis factor usually results in huge harmful effects on cardiac injury and dysfunction. In our previous study (PMID: 33294289), We observe a series of differential expressed genes between transcription and translation, which may be attributed to the hypoxia-specific binding affinity of Nuclear cap-binding subunit 3 (NCBP3) at 5’ un-translation region of target genes. But the underlying molecular mechanism of NCBP3 for gene translation modulation remains unclear. Here, we conducted RIP-seq of N6-Methyladenosine methylation in H9C2 cells with the conditions of normoxic, hypoxic and with additional NCBP3 knockdown.

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N6-methyladenosine Modulates Messenger RNA Translation Efficiency

Project description:N6-methyladenosine (m6A) is the most abundant internal messenger (mRNA) modification in mammalian mRNA. This modification is reversible and non-stoichiometric, which potentially adds an additional layer of variety and dynamic control of mRNA metabolism. The m6A-modified mRNA can be selectively recognized by the YTH family “reader” proteins. The preferential binding of m6A-containing mRNA by YTHDF2 is known to reduce the stability of the target transcripts; however, the exact effects of m6A on translation has yet to be elucidated. Here we show that another m6A reader protein, YTHDF1, promotes ribosome loading of its target transcripts. YTHDF1 forms a complex with translation initiation factors to elevate the translation efficiency of its bound mRNA. In a unified mechanism of translation control through m6A, the YTHDF2-mediated decay controls the lifetime of target transcripts; whereas, the YTHDF1-based translation promotion increases the translation efficiency to ensure effective protein production from relatively short-lived transcripts that are marked by m6A. PAR-CLIP and RIP was used to identify YTHDF1 binding sites followed by ribosome profling and RNA seq to assess the consequences of YTHDF1 siRNA knock-down

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YTHDF3 improves translation initiation of mRNAs with N6-methyladenosine methylation at 5’ untranslated region by facilitating eIF2AK2 recruitment in oxaliplatin-resistant colorectal cancer - RIP-seq dataset

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Fingerstick Blood-Test for Rapid Estimation of Absorbed Radiation Dose

Project description:Fingerstick Blood-Test for Rapid Estimation of Absorbed Radiation Dose

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Phase II for N6-methyladenosine RNA modification-based biodosimeters for absorbed ionizing radiation dose estimation

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Widespread N6-methyladenosine-dependent RNA Structural Switches Regulate RNA-Protein Interactions

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FMRP facilitates the nuclear export of N6-methyladenosine-containing mRNAs

Project description:FMRP facilitates the nuclear export of N6-methyladenosine-containing mRNAs.

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