Enhanced Differentiation of Isomeric RNA Modifications

The possibility of using ion mobility spectrometry (IMS) to differentiate different sizes or shapes holds a great potential to improve the detection of isomeric compounds. However, due to the lack of sensitivity and inadequate resolution, IMS has not been fully utilized in the analysis of various types of isomers, including RNA modifications. The goals of this study are to explore a way to achieve a more effective IM separation by reducing the size of ions prior to the IM measurements, and apply the improvement to enhance the accuracy for identifying specific isomeric RNA modifications. Using RNA methylation as an isomeric model, the proposed method can lower the required resolution by approximately 20%. The benefits of using the proposed method include adding the result of IM measurements as an extra dimension to the data set, such that the accuracy for the identification of isomeric RNA modifications is improved. In comparison to the results obtained from using the conventional MS/MS method on the same platform, there is no significant loss of ion signals when the proposed method was used. The proposed method is expected to be applicable to other types of isomeric compounds. Also, the same methodology is applicable on other ion mobility platforms.


  • Wang H, Todd DA, Chiu NH*. Enhanced differentiation of isomeric RNA modifications by reducing the size of ions in ion mobility mass spectrometric measurements. J. Anal. Sci. Technol., 11, 46-56(2020).