Atxn2l, also known as Ataxin-2-like, is involved in multiple biological processes. It functions as a master regulator of rhythmic translation along with ATXN2, with their oscillating phase separation in the suprachiasmatic nucleus modulating circadian rhythms [1]. It also participates in RNA surveillance at stress granules [2]. Additionally, it is associated with pathways like the JAK-STAT signaling pathway when fused with JAK2 in cutaneous CD4 positive T-cell lymphoma [4].

In Atxn2l-ablated mice, absence of the gene triggers mid-gestational embryonic lethality, with female animals more strongly affected. Homozygous mutants show reduced weight and development stages, brain lamination defects and apoptosis. Aged heterozygotes show no locomotor deficits or weight loss. Null mutants try to maximize Atxn2l expression, which is prevented by nutrient abundance in vitro. Mouse embryonal fibroblast cells show more multinucleated giant cells upon ATXN2L deficiency [2]. In gastric cancer, ATXN2L promotes cell invasiveness and oxaliplatin resistance, and can be upregulated by epidermal growth factor via the PI3K/Akt signaling [3].

In conclusion, Atxn2l is essential for embryogenesis. Its functions in neurodegenerative diseases and neuroprotective therapies are yet to be fully understood. In cancer, especially gastric cancer, it has a role in promoting cancer-related phenotypes such as invasion and chemoresistance. The study of Atxn2l through gene-knockout mouse models has provided insights into its biological functions and its potential implications in disease.

References:

1. Zhuang, Yanrong, Li, Zhiyuan, Xiong, Shiyue, Yang, Xuerui, Lin, Yi. 2023. Circadian clocks are modulated by compartmentalized oscillating translation. In Cell, 186, 3245-3260.e23. doi:10.1016/j.cell.2023.05.045. https://pubmed.ncbi.nlm.nih.gov/37369203/

2. Key, Jana, Harter, Patrick N, Sen, Nesli-Ece, Auburger, Georg, Gispert, Suzana. 2020. Mid-Gestation lethality of Atxn2l-Ablated Mice. In International journal of molecular sciences, 21, . doi:10.3390/ijms21145124. https://pubmed.ncbi.nlm.nih.gov/32698485/

3. Lin, Li, Li, Xiaoyin, Pan, Changqie, Liao, Yulin, Liao, Wangjun. 2019. ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance. In Cell death & disease, 10, 173. doi:10.1038/s41419-019-1362-2. https://pubmed.ncbi.nlm.nih.gov/30787271/

4. Panagopoulos, Ioannis, Gorunova, Ludmila, Spetalen, Signe, Micci, Francesca, Heim, Sverre. 2017. Fusion of the genes ataxin 2 like, ATXN2L, and Janus kinase 2, JAK2, in cutaneous CD4 positive T-cell lymphoma. In Oncotarget, 8, 103775-103784. doi:10.18632/oncotarget.21790. https://pubmed.ncbi.nlm.nih.gov/29262599/