Samd4b, also known as Smaug2, is a member of the SAMD4 protein family, which are novel RNA-binding proteins. It contains a sterile alpha motif (SAM) domain, allowing it to bind to specific target mRNAs through stem-loop structures (Smaug recognition elements, SREs), regulating mRNA stability, degradation, and translation. It is involved in various biological processes and pathological conditions, such as neural development, mitochondrial function, and cancer [2,4,6,7].

In hepatocellular carcinoma, a synergistic immunochemotherapy targeting the SAMD4B-APOA2-PD-L1 axis was proposed. Reduced mutations of upstream genes NOTCH1 and NOTCH2 increase SAMD4B, which affects APOA2 mRNA instability through 2'-O-Methylation modification at the C-terminus. Decreased APOA2 then attenuates PD-L1 levels, improving the immune microenvironment and achieving an antitumor effect [1]. In colorectal cancer, miR-451 suppresses the malignancy of cancer cells by targeting Samd4b, inhibiting proliferation, migration, and promoting apoptosis [3]. Also, in embryos fathered by obese males, Samd4b was significantly upregulated, suggesting a potential link between paternal obesity and gene expression changes in pre-implantation embryos [5].

In summary, Samd4b plays crucial roles in regulating mRNA-related processes and is involved in multiple biological and disease-related contexts, such as cancer and the impact of paternal obesity on embryos. Studies on Samd4b, including those potentially using gene knockout or conditional knockout mouse models, contribute to understanding its functions in these specific areas, providing insights for potential therapeutic strategies in related diseases [1,3,5].

References:

1. Qi, Feng, Zhang, Jian, Li, Jia, Cui, Wenguo, Xia, Jinglin. 2024. Synergistic immunochemotherapy targeted SAMD4B-APOA2-PD-L1 axis potentiates antitumor immunity in hepatocellular carcinoma. In Cell death & disease, 15, 421. doi:10.1038/s41419-024-06699-2. https://pubmed.ncbi.nlm.nih.gov/38886351/

2. Luo, Na, Li, Guan, Li, Yongqing, Deng, Yun, Wu, Xiushan. . SAMD4B, a novel SAM-containing protein, inhibits AP-1-, p53- and p21-mediated transcriptional activity. In BMB reports, 43, 355-61. doi:. https://pubmed.ncbi.nlm.nih.gov/20510020/

3. Wu, Chunrong, Liu, Xiaohu, Li, Bo, Peng, Chunfang, Xiang, Debing. 2021. miR‑451 suppresses the malignant characteristics of colorectal cancer via targeting SAMD4B. In Molecular medicine reports, 24, . doi:10.3892/mmr.2021.12196. https://pubmed.ncbi.nlm.nih.gov/34109425/

4. Wang, Xin-Ya, Zhang, Li-Na. 2023. RNA binding protein SAMD4: current knowledge and future perspectives. In Cell & bioscience, 13, 21. doi:10.1186/s13578-023-00968-x. https://pubmed.ncbi.nlm.nih.gov/36732864/

5. Bernhardt, Laura, Dittrich, Marcus, El-Merahbi, Rabih, Haaf, Thomas, El Hajj, Nady. 2021. A genome-wide transcriptomic analysis of embryos fathered by obese males in a murine model of diet-induced obesity. In Scientific reports, 11, 1979. doi:10.1038/s41598-021-81226-3. https://pubmed.ncbi.nlm.nih.gov/33479343/

6. Fernández-Alvarez, Ana J, Gabriela Thomas, María, Pascual, Malena L, Casado, Marta, Boccaccio, Graciela L. 2022. Smaug1 membrane-less organelles respond to AMPK and mTOR and affect mitochondrial function. In Journal of cell science, 135, . doi:10.1242/jcs.253591. https://pubmed.ncbi.nlm.nih.gov/34859817/

7. Fernández-Alvarez, Ana Julia, Pascual, Malena Lucía, Boccaccio, Graciela Lidia, Thomas, María Gabriela. 2016. Smaug variants in neural and non-neuronal cells. In Communicative & integrative biology, 9, e1139252. doi:10.1080/19420889.2016.1139252. https://pubmed.ncbi.nlm.nih.gov/27195061/