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Regulation of the parental gene GRM4 by circGrm4 RNA transcript and glutamate-mediated neurovascular toxicity in eyes.
- Source :
-
Molecular and cellular biochemistry [Mol Cell Biochem] 2021 Feb; Vol. 476 (2), pp. 663-673. Date of Electronic Publication: 2020 Oct 19. - Publication Year :
- 2021
-
Abstract
- Epigenetic memory plays crucial roles in gene regulation. It not only modulates the expression of specific genes but also has ripple effects on transcription as well as translation of other genes. Very often an alteration in expression occurs either via methylation or demethylation. In this context, "1-carbon metabolism" assumes a special significance since its dysregulation by higher levels of homocysteine; Hcy (known as hyperhomocysteinemia; HHcy), a byproduct of "1-Carbon Metabolism" during methionine biosynthesis leads to serious implications in cardiovascular, renal, cerebrovascular systems, and a host of other conditions. Currently, the circular RNAs (circRNAs) generated via non-canonical back-splicing events from the pre-mRNA molecules are at the center stage for their essential roles in diseases via their epigenetic manifestations. We recently identified a circular RNA transcript (circGRM4) that is significantly upregulated in the eye of cystathionine β-synthase-deficient mice. We also discovered a concurrent over-expression of the mGLUR4 receptor in the eyes of these mice. In brief, circGRM4 is selectively transcribed from its parental mGLUR4 receptor gene (GRM4) functions as a "molecular-sponge" for the miRNAs and results into excessive turnover of the mGLUR4 receptor in the eye in response to extremely high circulating glutamate concentration. We opine that this epigenetic manifestation potentially predisposes HHcy people to retinovascular malfunctioning.
- Subjects :
- Animals
Cystathionine beta-Synthase metabolism
Endothelial Cells metabolism
Epigenesis, Genetic
Eye Diseases chemically induced
Eye Diseases genetics
Eye Diseases metabolism
Eye Diseases pathology
Homocysteine metabolism
Humans
Hyperhomocysteinemia genetics
MicroRNAs genetics
RNA, Circular genetics
Receptors, Metabotropic Glutamate genetics
Vascular Diseases chemically induced
Vascular Diseases genetics
Vascular Diseases metabolism
Vascular Diseases pathology
Cystathionine beta-Synthase genetics
Eye blood supply
Eye metabolism
Glutamic Acid metabolism
MicroRNAs metabolism
RNA, Circular metabolism
Receptors, Metabotropic Glutamate metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4919
- Volume :
- 476
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33074445
- Full Text :
- https://doi.org/10.1007/s11010-020-03934-0