The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons

Abstract

Cerebral ischaemia‒reperfusion injury (IRI), during which neurons undergo oxygen-glucose deprivation/reoxygenation (OGD/R), is a notable pathological process in many neurological diseases. N1-methyladenosine (m1A) is an RNA modification that can affect gene expression and RNA stability. The m1A landscape and potential functions of m1A modification in neurons remain poorly understood. We explored RNA (mRNA, lncRNA, and circRNA) m1A modification in normal and OGD/R-treated mouse neurons and the effect of m1A on diverse RNAs. We investigated the m1A landscape in primary neurons, identified m1A-modified RNAs, and found that OGD/R increased the number of m1A RNAs. m1A modification might also affect the regulatory mechanisms of noncoding RNAs, e.g., lncRNA–RNA binding proteins (RBPs) interactions and circRNA translation. We showed that m1A modification mediates the circRNA/lncRNA‒miRNA–mRNA competing endogenous RNA (ceRNA) mechanism and that 3' untranslated region (3’UTR) modification of mRNAs can hinder miRNA–mRNA binding. Three modification patterns were identified, and genes with different patterns had intrinsic mechanisms with potential m1A-regulatory specificity. Systematic analysis of the m1A landscape in normal and OGD/R neurons lays a critical foundation for understanding RNA modification and provides new perspectives and a theoretical basis for treating and developing drugs for OGD/R pathology-related diseases.

miR-423 sponged by lncRNA NORHA inhibits granulosa cell apoptosis

“…LncRNAs are ncRNAs that are more than 200 nt in length. They often block the inhibition of miRNAs on target mRNAs by acting as ceRNAs of miRNAs in the cytoplasm [ 10 , 46 ]. NORHA , a cytoplasmic lncRNA in sow GCs, is a potential ceRNA of multiple miRNAs that are differentially expressed during sow FA [ 23 ].…”

“…Although miRNAs were the first ncRNAs to be discovered, they are still the most studied because of their wide distribution, conserved sequences, simultaneous actions on multiple target mRNAs, and crucial functions [ 2 , 4 , 8 ]. Additionally, the main mechanism of action of other popular ncRNAs, such as circular RNAs (circRNAs) [ 5 , 9 , 10 ], involves acting as competing endogenous RNAs (ceRNAs) of miRNAs.…”

The highly abundant mRNA m1A modification: a new layer of gene regulation in dinoflagellates

“…microRNA has been reported to show differential expression in dinoflagellates under stress conditions, suggesting it could be used to regulate gene expression at the post-transcriptional level (Shi, Lin et al, 2017). Recent study on m 1 A profiling in primary neurons has shown that m 1 A modification in the 3’ UTRs of mRNA could prevent the binding of miRNA, resulting in enhanced gene expression (Baumgarten, Bayer et al, 2013, Zhang, Yi et al, 2023). microRNA generally mediates transcript degradation and/or translation repression by binding to 3’ UTR of mRNA (Shang, Lee et al, 2023, Song, Li et al, 2019).…”