Csde1-KO Mouse

Csde1, also known as cold shock domain containing E1, is an RNA-binding protein that plays a key role in translational reprogramming. It can act as a "protein-RNA connector", binding to RNAs and collaborating with other protein regulators to determine the fate of numerous RNAs. This includes promoting or repressing RNA translation, as well as increasing or decreasing RNA abundance. Csde1 is involved in multiple biological processes and is associated with various pathways, such as the miRNA-mediated gene regulation pathway and the Wnt/β-catenin signaling pathway [1,2,3].

Genetic mutants and morphants in zebrafish demonstrated that depletion of csde1 impaired the production of hematopoietic stem and progenitor cells (HSPCs). Mechanistically, Csde1 binds to ctnnb1 mRNAs, regulating the translation (but not the stability) of ctnnb1 mRNA, enhancing β-catenin protein level and Wnt signal transduction activities, thus promoting HSPC generation [2]. In primary mouse keratinocytes, depletion of CSDE1 led to senescence bypass, cell immortalization, and tumor formation, indicating CSDE1 behaves as a tumor suppressor. It promotes oncogene-induced senescence (OIS) through enhancing the stability of senescence-associated secretory phenotype (SASP) factor mRNAs and repressing Ybx1 mRNA translation [4].

In conclusion, Csde1 is a crucial regulator in translational reprogramming and various biological processes. Studies using gene-depletion models in zebrafish and mouse keratinocytes have revealed its role in HSPC generation and OIS, respectively. These findings contribute to our understanding of the biological functions of Csde1 and its potential implications in cancer and hematopoietic-related diseases.

References:

1. Guo, Ao-Xiang, Cui, Jia-Jia, Wang, Lei-Yun, Yin, Ji-Ye. 2020. The role of CSDE1 in translational reprogramming and human diseases. In Cell communication and signaling : CCS, 18, 14. doi:10.1186/s12964-019-0496-2. https://pubmed.ncbi.nlm.nih.gov/31987048/

2. Li, Ying, Li, Can, Liu, Mengyao, Liu, Feng, Wang, Lu. 2023. The RNA-binding protein CSDE1 promotes hematopoietic stem and progenitor cell generation via translational control of Wnt signaling. In Development (Cambridge, England), 150, . doi:10.1242/dev.201890. https://pubmed.ncbi.nlm.nih.gov/37874038/

3. Kakumani, Pavan Kumar, Harvey, Louis-Mathieu, Houle, François, Gebauer, Fátima, Simard, Martin J. 2020. CSDE1 controls gene expression through the miRNA-mediated decay machinery. In Life science alliance, 3, . doi:10.26508/lsa.201900632. https://pubmed.ncbi.nlm.nih.gov/32161113/

4. Avolio, Rosario, Inglés-Ferrándiz, Marta, Ciocia, Annagiulia, Ribó, Anna, Gebauer, Fátima. . Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1. In Cell reports, 38, 110211. doi:10.1016/j.celrep.2021.110211. https://pubmed.ncbi.nlm.nih.gov/35021076/