Pym1-KO Mouse

PYM1, also known as PYM, is an important factor involved in the regulation of mRNA fate. It can bind both the ribosome and the RBM8A/MAGOH heterodimer of the Exon Junction Complex (EJC) core. EJC, deposited upstream of exon-exon junctions during pre-mRNA splicing, modulates mRNA fate at multiple post-transcriptional steps, and PYM1 is involved in an EJC disassembly mechanism, which is crucial for translation-independent EJC destabilization [1].

In human embryonic kidney 293 (HEK293) cells, acute reduction of PYM1 levels modestly inhibits nonsense-mediated mRNA decay and stabilizes certain mRNAs. These mRNAs localize to endoplasmic reticulum-associated TIS-granules and are characterized by fewer and longer exons [1]. Also, in flaviviral infections, PYM1 has antiviral roles. Flavivirus capsids interact with PYM1, and depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that the virus sequesters PYM1 to protect viral RNA from decay [2].

In summary, PYM1 is a key factor in regulating mRNA fate through its role in EJC disassembly. Its function has implications in processes like nonsense-mediated mRNA decay and in antiviral defense mechanisms, especially in the context of flaviviral infections. Studies on PYM1 help to understand the complex interplay between host cells and viruses at the post-transcriptional regulation level.

References:

1. Sanjeev, Manu, Woodward, Lauren A, Schiff, Michael L, Bundschuh, Ralf, Singh, Guramrit. 2025. PYM1 limits non-canonical Exon Junction Complex occupancy in a gene architecture dependent manner to tune mRNA expression. In bioRxiv : the preprint server for biology, , . doi:10.1101/2025.03.13.643037. https://pubmed.ncbi.nlm.nih.gov/40161626/

2. Li, Minghua, Johnson, Jeffrey R, Truong, Billy, Cherry, Sara, Ramage, Holly. 2019. Identification of antiviral roles for the exon-junction complex and nonsense-mediated decay in flaviviral infection. In Nature microbiology, 4, 985-995. doi:10.1038/s41564-019-0375-z. https://pubmed.ncbi.nlm.nih.gov/30833725/

3. Gehring, Niels H, Lamprinaki, Styliani, Kulozik, Andreas E, Hentze, Matthias W. . Disassembly of exon junction complexes by PYM. In Cell, 137, 536-48. doi:10.1016/j.cell.2009.02.042. https://pubmed.ncbi.nlm.nih.gov/19410547/