The roles and therapeutic implications of messenger RNA internal N 7 ‐methylguanosine and N 6 ‐methyladenosine modifications in chemoresistance

Abstract

Resistance to chemotherapy is responsible for the death of most cancer patients. RNA modifications are key players in post-transcriptional gene regulation and their dysreg-ulations contribute to tumor initiation, progression, and resistance to chemotherapy. Despite the identification of over 170 chemical modifications in nearly all types of RNAs, the biological functions and underlying mechanisms of the vast majority of RNA modifications remain elusive in the context of tumorigenesis and drug resistance. N 6-methyladenosine (m 6 A) is the most prevalent internal modification in eukaryotic messenger RNAs (mRNAs). The characterization of proteins that deposit, remove, and recognize mRNA m 6 A marks, as writers, erasers and readers, respectively, has revealed the profound roles of m 6 A in determining mRNA fates during both physiological and pathological processes. Besides m 6 A, another commonly observed positively charged modification is N 7-methylguanosine (m 7 G), which is ubiquitously located at the 5′ cap of mRNAs. This m 7 G cap is fundamental to mRNA stability, export, and translation. Meanwhile, multiple independent studies have revealed that m 7 G modification could also be introduced internally onto mRNAs # Zhicong Zhao and Ying Qing contributed equally. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.