Dysregulation of the Epitranscriptomic Mark m 1 A in Ischemic Stroke.

Autor: Chokkalla AK; Department of Neurological Surgery, University of Wisconsin, Madison, WI, 53792, USA., Pajdzik K; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA., Dou X; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA., Dai Q; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA., Mehta SL; Department of Neurological Surgery, University of Wisconsin, Madison, WI, 53792, USA., Arruri V; Department of Neurological Surgery, University of Wisconsin, Madison, WI, 53792, USA., Vemuganti R; Department of Neurological Surgery, University of Wisconsin, Madison, WI, 53792, USA. vemuganti@neurosurgery.wisc.edu.; William S. Middleton Memorial Veteran Administration Hospital, Madison, WI, USA. vemuganti@neurosurgery.wisc.edu.
Jazyk: angličtina
Zdroj: Translational stroke research [Transl Stroke Res] 2023 Dec; Vol. 14 (6), pp. 806-810. Date of Electronic Publication: 2022 Jun 23.
DOI: 10.1007/s12975-022-01056-x
Abstrakt: Methylation of adenosine at N1 position yields N 1 -methyladenosine (m 1 A), which is an epitranscriptomic modification that regulates mRNA metabolism. Recent studies showed that altered m 1 A methylation promotes acute and chronic neurological diseases. We currently evaluated the effect of focal ischemia on cerebral m 1 A methylome and its machinery. Adult male C57BL/6J mice were subjected to transient middle cerebral artery occlusion, and the peri-infarct cortex was analyzed at 12 h and 24 h of reperfusion. The bulk abundance of m 1 A was measured by mass spectrometry and dot blot, and transcriptome-wide m 1 A alterations were profiled using antibody-independent m 1 A-quant-seq. Expression of the m 1 A writers and erasers was estimated by real-time PCR. Ischemia significantly decreased m 1 A levels and concomitantly upregulated m 1 A demethylase alkB homolog 3 at 24 h of reperfusion compared to sham. Transcriptome-wide profiling showed differential m 1 A methylation at 14 sites (8 were hypo- and 6 were hypermethylated). Many of those are located in the 3'-UTRs of unannotated transcripts proximal to the genes involved in regulating protein complex assembly, circadian rhythms, chromatin remodeling, and chromosome organization. Using several different approaches, we show for the first time that m 1 A epitranscriptomic modification in RNA is highly sensitive to cerebral ischemia.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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