Tissue-specific alternative splicing separates the catalytic and cell signaling functions of human leucyl-tRNA synthetase

Baymiller, Maxwell; Nordick, Benjamin; Forsyth, Connor M.; Martinis, Susan A.

doi:10.1016/j.jbc.2022.101757

Cited by 3 publications

(2 citation statements)

References 52 publications

(95 reference statements)

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“…Understanding the functions of tDRs may yield valuable insights into the mechanisms by which these molecules regulate gene expression and mediate cellular responses to hypoxia. 35 , 36 , 37 , 38 , 39 …”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of small noncoding RNA profiles in hypoxia-induced pulmonary hypertension (HPH) rat tissues

Wang,

Kuang,

Zhang

et al. 2024

iScience

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Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of small noncoding RNA profiles in hypoxia-induced pulmonary hypertension (HPH) rat tissues

Wang,

Kuang,

Zhang

et al. 2024

iScience

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“…These non-canonical functions are the regulation of gene expression, RNA splicing, tumorigenesis, angiogenesis, and immune response [ 31 , 32 ]. For instance, allergen-induced phosphorylation of lysyl-tRNA synthetase (KARS) triggers its release from the multi-AARS complex, induces conformational changes, and suppresses its translational activity while enhancing the orthogonal function of activating the transcription of immune genes [ 33 , 34 ]. Therefore, the 108 differential proteins in IARS1 V79L mice may arise from the unknown failed non-canonical functions of IARS due to the V79L mutation.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Pathological Analyses of IARS1-Deficient Mice: An IARS Disorder Model

Watanabe

Shishido

Kanehira

et al. 2023

IJMS

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Most mitochondrial diseases are hereditary and highly heterogeneous. Cattle born with the V79L mutation in the isoleucyl-tRNA synthetase 1 (IARS1) protein exhibit weak calf syndrome. Recent human genomic studies about pediatric mitochondrial diseases also identified mutations in the IARS1 gene. Although severe prenatal-onset growth retardation and infantile hepatopathy have been reported in such patients, the relationship between IARS mutations and the symptoms is unknown. In this study, we generated hypomorphic IARS1V79L mutant mice to develop an animal model of IARS mutation-related disorders. We found that compared to wild-type mice, IARSV79L mutant mice showed a significant increase in hepatic triglyceride and serum ornithine carbamoyltransferase levels, indicating that IARS1V79L mice suffer from mitochondrial hepatopathy. In addition, siRNA knockdown of the IARS1 gene decreased mitochondrial membrane potential and increased reactive oxygen species in the hepatocarcinoma-derived cell line HepG2. Furthermore, proteomic analysis revealed decreased levels of the mitochondrial function-associated protein NME4 (mitochondrial nucleoside diphosphate kinase). Concisely, our mutant mice model can be used to study IARS mutation-related disorders.

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Leucyl-tRNA Synthetase Contributes to Muscle Weakness through Mammalian Target of Rapamycin Complex 1 Activation and Autophagy Suppression in a Mouse Model of Duchenne Muscular Dystrophy

You,

Karaman,

Reyes-Ordoñez

et al. 2024

The American Journal of Pathology

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Tissue-specific alternative splicing separates the catalytic and cell signaling functions of human leucyl-tRNA synthetase

Cited by 3 publications

References 52 publications

Comprehensive characterization of small noncoding RNA profiles in hypoxia-induced pulmonary hypertension (HPH) rat tissues

Comprehensive characterization of small noncoding RNA profiles in hypoxia-induced pulmonary hypertension (HPH) rat tissues

Molecular and Pathological Analyses of IARS1-Deficient Mice: An IARS Disorder Model

Leucyl-tRNA Synthetase Contributes to Muscle Weakness through Mammalian Target of Rapamycin Complex 1 Activation and Autophagy Suppression in a Mouse Model of Duchenne Muscular Dystrophy

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