Rpl5, encoding ribosomal protein L5, is a crucial gene involved in ribosome biogenesis, an essential process for protein synthesis [1,5,6]. It may also be associated with multiple biological pathways and diseases, highlighting its overall biological importance. Genetic models, such as mouse models, are valuable for studying Rpl5's functions [1].

An inducible mouse model using tetracycline-induced down-regulation of Rpl5 was created to mimic Diamond-Blackfan anemia (DBA) symptoms. After doxycycline treatment, shRNA Rpl5+/- adult mice developed mild anemia, reticulocytopenia, and bone marrow erythroblastopenia, making them a useful DBA model [1]. In DBA patient-derived lymphoblastoid cells and RPL5-knocked down CD34+ cells, there were DNA double-strand break (DSB) repair defects, with RPL5-KD increasing end-joining pathways [6]. In colon cancer, knockdown of RPL5 significantly inhibited cell proliferation and migration, arrested the cell cycle in G0/G1 phase, and down-regulated proteins in the MAPK/ERK signaling pathway [2]. In breast cancer, overexpression of RPL5 inhibited cell proliferation, induced endoplasmic reticulum stress (ERS), and suppressed autophagy via regulating E2F1 [3]. Olaparib, a PARP inhibitor, activates p53 in a RPL5/RPL11-dependent manner through nucleolar stress [4].

In conclusion, Rpl5 plays vital roles in ribosome biogenesis, and its dysregulation is associated with DBA, colon cancer, breast cancer, and response to certain cancer therapies. The Rpl5-inducible mouse model contributes significantly to understanding the pathological mechanisms of DBA. These findings from model-based research enhance our understanding of Rpl5's functions and its implications in disease, potentially guiding new therapeutic strategies.

References:

1. Kazerounian, Shideh, Yuan, Daniel, Alexander, Matthew S, Beggs, Alan H, Gazda, Hanna T. 2019. Rpl5-Inducible Mouse Model for Studying Diamond-Blackfan Anemia. In Discoveries (Craiova, Romania), 7, e96. doi:10.15190/d.2019.9. https://pubmed.ncbi.nlm.nih.gov/32309614/

2. Zhang, Huahua, Liu, Junli, Dang, Qingqing, Liu, Yong, Han, Jiming. 2022. Ribosomal protein RPL5 regulates colon cancer cell proliferation and migration through MAPK/ERK signaling pathway. In BMC molecular and cell biology, 23, 48. doi:10.1186/s12860-022-00448-z. https://pubmed.ncbi.nlm.nih.gov/36384455/

3. Ma, Xiaoping, Li, Yan, Zhao, Bing. . Ribosomal protein L5 (RPL5)/ E2F transcription factor 1 (E2F1) signaling suppresses breast cancer progression via regulating endoplasmic reticulum stress and autophagy. In Bioengineered, 13, 8076-8086. doi:10.1080/21655979.2022.2052672. https://pubmed.ncbi.nlm.nih.gov/35293275/

4. Han, Tao, Tong, Jing, Wang, Mengxin, Hao, Qian, Zhou, Xiang. 2022. Olaparib Induces RPL5/RPL11-Dependent p53 Activation via Nucleolar Stress. In Frontiers in oncology, 12, 821366. doi:10.3389/fonc.2022.821366. https://pubmed.ncbi.nlm.nih.gov/35719981/

5. Dorenkamp, Moritz, Porret, Naomi, Diepold, Miriam, Rovó, Alicia. 2023. A De Novo Frameshift Mutation in RPL5 with Classical Phenotype Abnormalities and Worsening Anemia Diagnosed in a Young Adult-A Case Report and Review of the Literature. In Medicina (Kaunas, Lithuania), 59, . doi:10.3390/medicina59111953. https://pubmed.ncbi.nlm.nih.gov/38004002/

6. DeCleene, Nicholas F, Asik, Elif, Sanchez, Anthony, Wang, Yu-Hsiu, Bertuch, Alison A. 2024. RPS19 and RPL5, the most commonly mutated genes in Diamond Blackfan anemia, impact DNA double-strand break repair. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.10.10.617668. https://pubmed.ncbi.nlm.nih.gov/39416207/