Rbm7-KO Mouse

Rbm7, a component of the Nuclear Exosome Targeting (NEXT) complex, plays diverse roles in cells. It is involved in RNA surveillance, regulating the degradation of nuclear noncoding RNAs by guiding the RNA exosome [6,7,8]. Rbm7 also activates the positive transcription elongation factor b (P-TEFb), which is crucial for RNA polymerase II release from promoter-proximal pausing and expression of DNA damage response genes, thus promoting cell viability after genotoxic stress [4,5].

In breast cancer, Rbm7 deficiency promotes metastasis. Rbm7-depleted breast cancer cells show increased lung metastasis potential, enhanced migration, invasion, and angiogenesis. Mechanistically, Rbm7 controls the MFGE8 splicing switch, favoring the production of MFGE8-L which inhibits cell migration and invasion, while the truncated MFGE8-S has the opposite effect. Also, Rbm7 negatively regulates the NF-κB cascade [1]. In lung fibrosis, increased Rbm7 expression in lung epithelial cells promotes the degradation of the long non-coding RNA NEAT1, impairs DNA repair, triggers apoptosis, and recruits fibrosis-promoting monocytes, leading to the onset of fibrosis [2,3].

In conclusion, Rbm7 is essential for RNA-related processes and cell survival under stress. Its dysregulation is associated with breast cancer metastasis and lung fibrosis. Studies using models like Rbm7-depleted breast cancer cells and mouse models of lung fibrosis have been crucial in uncovering these disease-related roles of Rbm7, providing insights into potential therapeutic targets for these diseases.

References:

1. Huang, Fang, Dai, Zhenwei, Yu, Jinmiao, Qi, Yangfan, Wang, Yang. 2024. RBM7 deficiency promotes breast cancer metastasis by coordinating MFGE8 splicing switch and NF-kB pathway. In eLife, 13, . doi:10.7554/eLife.95318. https://pubmed.ncbi.nlm.nih.gov/38995840/

2. Fukushima, Kiyoharu, Akira, Shizuo. . Novel insights into the pathogenesis of lung fibrosis: the RBM7-NEAT1-CXCL12-SatM axis at fibrosis onset. In International immunology, 33, 659-663. doi:10.1093/intimm/dxab034. https://pubmed.ncbi.nlm.nih.gov/34165514/

3. Hammad, Hamida, Lambrecht, Bart N. . Rbm7 in Structural Cells: A NEAT Way to Control Fibrosis. In Immunity, 52, 429-431. doi:10.1016/j.immuni.2020.02.008. https://pubmed.ncbi.nlm.nih.gov/32187513/

4. Le May, Nicolas, Coin, Frédéric. . Activation of P-TEFb by RBM7: To Live or Let Die. In Molecular cell, 74, 223-224. doi:10.1016/j.molcel.2019.03.039. https://pubmed.ncbi.nlm.nih.gov/31002802/

5. Bugai, Andrii, Quaresma, Alexandre J C, Friedel, Caroline C, Dölken, Lars, Barborič, Matjaž. 2019. P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress. In Molecular cell, 74, 254-267.e10. doi:10.1016/j.molcel.2019.01.033. https://pubmed.ncbi.nlm.nih.gov/30824372/

6. Puno, M Rhyan, Lima, Christopher D. . Structural basis for RNA surveillance by the human nuclear exosome targeting (NEXT) complex. In Cell, 185, 2132-2147.e26. doi:10.1016/j.cell.2022.04.016. https://pubmed.ncbi.nlm.nih.gov/35688134/

7. Tiedje, Christopher, Lubas, Michal, Tehrani, Mohammad, Kotlyarov, Alexey, Gaestel, Matthias. 2014. p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex. In RNA (New York, N.Y.), 21, 262-78. doi:10.1261/rna.048090.114. https://pubmed.ncbi.nlm.nih.gov/25525152/

8. Hrossova, Dominika, Sikorsky, Tomas, Potesil, David, Stefl, Richard, Vanacova, Stepanka. 2015. RBM7 subunit of the NEXT complex binds U-rich sequences and targets 3'-end extended forms of snRNAs. In Nucleic acids research, 43, 4236-48. doi:10.1093/nar/gkv240. https://pubmed.ncbi.nlm.nih.gov/25852104/