Dtd2-KO Mouse

Dtd2, short for D-aminoacyl-tRNA deacylase 2, is an enzyme with a crucial role in translation quality control. It specifically acts on D-aminoacyl-tRNAs, removing N-ethyl adducts formed on them, which are generated as a result of anaerobic stress in plants [2]. Dtd2 is of archaeal origin and is conserved from streptophyte algae to land plants, suggesting its importance in the emergence and evolution of land plants [2]. It is also involved in safeguarding the translation machinery from the harmful effects of misaminoacylated D-aminoacyl-tRNAs [3].

In plants, Dtd2 knockout studies have shown that it is essential for protecting plants from the toxicity of aldehydes such as acetaldehyde, formaldehyde, and methylglyoxal. These aldehydes can generate adducts with aminoacyl-tRNAs, and only Dtd2 can remove the stable D-aminoacyl adducts on tRNA, rescuing plants from these system-generated aldehydes. Loss of the Dtd2 gene renders plants susceptible to these toxic aldehydes [4]. In addition, in the context of Sjögren disease, IgG against a peptide from Dtd2 binds more in anti-SSA antibody negative Sjögren disease cases compared to sicca-controls and combined controls, and also binds more in participants with positive focus score (FS) in labial salivary gland biopsies, indicating its potential as a biomarker for diagnosis [1,5].

In conclusion, Dtd2 is crucial for maintaining translation accuracy and protecting plants from aldehyde-induced stress. Its role as a potential biomarker in Sjögren disease adds to its significance. The gene knockout studies in plants have been instrumental in revealing its function in protecting against aldehyde toxicity, while its association with Sjögren disease provides new avenues for diagnosis in this autoimmune disorder [1,2,4,5].

References:

1. Parker, Maxwell, Zheng, Zihao, Lasarev, Michael R, Shelef, Miriam A, McCoy, Sara S. 2024. Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology. In Annals of the rheumatic diseases, 83, 1169-1180. doi:10.1136/ard-2023-224936. https://pubmed.ncbi.nlm.nih.gov/38702176/

2. Mazeed, Mohd, Singh, Raghvendra, Kumar, Pradeep, Kruparani, Shobha P, Sankaranarayanan, Rajan. 2021. Recruitment of archaeal DTD is a key event toward the emergence of land plants. In Science advances, 7, . doi:10.1126/sciadv.abe8890. https://pubmed.ncbi.nlm.nih.gov/33536220/

3. Ferri-Fioni, Maria-Laura, Fromant, Michel, Bouin, Anne-Pascale, Plateau, Pierre, Blanquet, Sylvain. 2006. Identification in archaea of a novel D-Tyr-tRNATyr deacylase. In The Journal of biological chemistry, 281, 27575-85. doi:. https://pubmed.ncbi.nlm.nih.gov/16844682/

4. Kumar, Pradeep, Roy, Ankit, Mukul, Shivapura Jagadeesha, Siddiqi, Imran, Sankaranarayanan, Rajan. 2024. A translation proofreader of archaeal origin imparts multi-aldehyde stress tolerance to land plants. In eLife, 12, . doi:10.7554/eLife.92827. https://pubmed.ncbi.nlm.nih.gov/38372335/

5. Parker, Maxwell, Zheng, Zihao, Lasarev, Michael, Shelef, Miriam A, McCoy, Sara S. 2023. Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren's disease and predict abnormal labial salivary gland pathology. In medRxiv : the preprint server for health sciences, , . doi:10.1101/2023.08.29.23294775. https://pubmed.ncbi.nlm.nih.gov/37693588/