AI Article Synopsis
- - RNA can be chemically modified through methylation, particularly at the N6-methyladenosine (mA) site on mRNA, which is regulated by the methyltransferase complex and removed by demethylases FTO and ALKBH5.
- - The outcome of mA-marked mRNA can either lead to its degradation or stabilization/translation, influenced largely by its interaction with specific proteins known as YTH domain-containing proteins.
- - New insights show that factors like metabolism and posttranslational modifications can affect the functioning and location of FTO and ALKBH5, indicating that mA methylation is a dynamic process that warrants further exploration in cancer and other health conditions.
Article Abstract
Similar to DNA and histone, RNA can also be methylated. In its most common form, a N6-methyladenosine (mA) chemical modification is introduced into nascent messenger ribonucleic acid (mRNA) by a specialized methyltransferase complex and removed by the RNA demethylases, Fat mass and obesity-associated (FTO), and ALKBH5. The fate of mA-marked mRNA is uniquely diverse, ranging from degradation to stabilization/translation, which has been suggested to be largely dependent on its interaction with the family of YT521-B homology (YTH) domain-containing proteins. Here, we highlight a series of control levers that impinge on the RNA demethylases. We present evidence to indicate that intermediary metabolism and various posttranslation modifications modulate the activity, stability, and the subcellular localization of FTO and ALKBH5, further dispelling the notion that mA methylation is not a dynamic process. We also discuss how examination of these underappreciated regulatory nodes adds a more nuanced view of the role of FTO and ALKBH5 and should guide their study in cancer and nonmalignant conditions alike.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572932 | PMC |
| http://dx.doi.org/10.1073/pnas.2317847121 | DOI Listing |
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