Messenger RNA (mRNA) regulates cell proliferation. The 5’- terminal ends of cellular mRNAs contain an m7GpppN cap, in which N can be any nucleotide. The RNA helicase eIF4A and the scaffold protein eukaryotic translation initiation factor 4G (eIF4G) and the capping protein eIF4E are part of the complex that loads the mRNAs onto the 40 S ribosomal subunit, together with eIF3. eIF4E has a crucial role in the regulation of translation.
4E-binding proteins (4E-BPs) block the interaction of eIF4E with eIF4G to negatively regulate the formation of the eIF4F complex.
RNA-based pharmaceutical therapeutics and vaccines are a new approach to treating chronic and rare diseases, including COVID-19. Fore example, the deregulation of translation control appears the cause of many cancer types. The expression of eIF4E influences cell growth and phenotype. The overexpression of eIF4E leads to accelerated cell division and malignant transformation.
Structural complexes between proteins and their substrates can be studied in the gas-phase to determine equilibrium dissociation constants. Brown et al., in 2007, showed that mass spectrometry allows the measurement of the apparent gas-phase equilibrium dissociation constants (Kd) values for the specific molecular binding events. The Kds of guanosine triphosphate (GTP), GMP, and cap derivatives interactions with eIF4E were determined.
Reference
Brown CJ, McNae I, Fischer PM, Walkinshaw MD; Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives. J Mol Biol (2007) 372 p.7-15. [PubMed]
Jin Wang, Bing Liang Alvin Chew, Yong Lai, Hongping Dong, Luang Xu, Seetharamsingh Balamkundu, Weiling Maggie Cai, Liang Cui, Chuan Fa Liu, Xin-Yuan Fu, Zhenguo Lin, Pei-Yong Shi, Timothy K. Lu, Dahai Luo, Samie R. Jaffrey, Peter C. Dedon; Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA. bioRxiv 683045. [Nucleic Acids Research]
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