Neurodevelopmental disorders associated variants in ADAT3 disrupt the activity of the ADAT2/ADAT3 tRNA deaminase complex and impair neuronal migration.
العنوان: | Neurodevelopmental disorders associated variants in ADAT3 disrupt the activity of the ADAT2/ADAT3 tRNA deaminase complex and impair neuronal migration. |
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المؤلفون: | Del-Pozo-Rodriguez J, Tilly P, Lecat R, Vaca HR, Mosser L, Balla T, Gomes MV, Ramos-Morales E, Brivio E, Salinas-Giégé T, VanNoy G, England EM, Lovgren AK, O'Leary M, Chopra M, Gable D, Alnuzha A, Kamel M, Almenabawy N, O'Donnell-Luria A, Neil JE, Gleeson JG, Walsh CA, Elkhateeb N, Selim L, Srivastava S, Nedialkova DD, Drouard L, Romier C, Bayam E, Godin JD |
المصدر: | MedRxiv : the preprint server for health sciences [medRxiv] 2024 Mar 05. Date of Electronic Publication: 2024 Mar 05. |
نوع المنشور: | Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
مستخلص: | The ADAT2/ADAT3 complex catalyzes the adenosine to inosine modification at the wobble position of eukaryotic tRNAs. Mutations in ADAT3 , the catalytically inactive subunit of the ADAT2/ADAT3 complex, have been identified in patients presenting with severe neurodevelopmental disorders (NDDs). Yet, the physiological function of ADAT2/ADAT3 complex during brain development remains totally unknown. Here we showed that maintaining a proper level of ADAT2/ADAT3 catalytic activity is required for correct radial migration of projection neurons in the developing mouse cortex. In addition, we not only reported 7 new NDD patients carrying biallelic variants in ADAT3 but also deeply characterize the impact of those variants on ADAT2/ADAT3 structure, biochemical properties, enzymatic activity and tRNAs editing and abundance. We demonstrated that all the identified variants alter both the expression and the activity of the complex leading to a significant decrease of I |
تواريخ الأحداث: | Date Created: 20240318 Latest Revision: 20240318 |
رمز التحديث: | 20240318 |
مُعرف محوري في PubMed: | PMC10942499 |
DOI: | 10.1101/2024.03.01.24303485 |
PMID: | 38496416 |
قاعدة البيانات: | MEDLINE |
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