Mepce-flox Mouse

MePCE, short for methylphosphate capping enzyme, is a crucial protein involved in multiple biological processes. It monomethylates the gamma phosphate at the 5' end of the 7SK noncoding RNA, protecting 7SK from degradation [1,2]. 7SK serves as a scaffold for assembling a snRNP complex that inhibits transcription by sequestering the positive elongation factor P-TEFb, thus playing a significant role in regulating RNA polymerase II (RNAP II) transcription [1,2].

In Drosophila, the Bin3 ortholog of MePCE has been studied. Bin3 mutant females showed reduced egg-laying rates and neuromuscular defects, which could be rescued by reducing P-TEFb activity, suggesting that MePCE promotes fecundity and neuromuscular function by repressing P-TEFb [1,2]. In human cells, a de novo MEPCE nonsense variant in a patient with global developmental delay and seizures led to decreased MEPCE, downregulation of LARP7 and 7SK snRNA, upregulation of HEXIM1, enhanced activation of P-TEFb, and increased expression of specific RNAP II-sensitive genes. Ectopic MEPCE protein expression rescued these changes [3].

In conclusion, MePCE is essential for 7SK RNA capping and stability, playing a key role in regulating P-TEFb-dependent transcription. Studies in Drosophila and human patient cells with MePCE-related mutations have revealed its importance in development and disease-associated processes such as neurodevelopmental disorders [1,2,3].