A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation

Pei, Wuhong; Chen, Zelin; Slevin, Claire C; Pettie, Kade; Wincovitch, Stephen; Program, Nisc Comparative Sequencing; Burgess, Shawn M.

doi:10.1101/678417

Cited by 2 publications

(2 citation statements)

References 64 publications

(68 reference statements)

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“…[38] GEMIN5 levels were increased with mutant TP53 and consistent with the previous zebrafish studies indicate that GEMIN5 is associated with TP53 regulation/ activation. [39] Studies have shown that normal TP53 decreases the expression of the NPAT through a G1 cell-cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

Study on mRNA expression of Cajal body – Gemini of coiled body proteins in head and neck squamous cell carcinoma

Thavarajah

Imaneul

Joshua

et al. 2020

IJMIO

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Objectives: The role of proteins of Cajal bodies (CB) and its identical twin, Gemini of coiled bodies (GEMs) in maintaining genomic integrity and its influence on the initiation, progression, and prognosis of head and neck squamous cell carcinoma (HNSCC) is gaining attention. We attempted to identify the CB and GEM-associated proteins (CB-GEMs) expression in HNSCC patients and study the influence of gender, TP53 mutation, age, and tobacco use on such expression. Material and Methods: TP53 mutation, tobacco use, gender, and mRNA levels of CB-GEM proteins of 520 HNSCC cases were collected and subjected to differential expression (DE) analysis. The resultant DE genes were used to create a transcriptional factor gene network using encode chip sequential data. Pathway analysis of the network was performed and presented. P ≤ 0.05 was taken as significant. Results: For smoking, the genes GEMIN8, FMR1, TRIM22, and FBL emerged as significantly DE genes. For gender, EAF1, GEMIN8, ZC3H8, TRIM22, FBL, LSG1, ZNF473, GMNC, GEMIN2, ISG20, Opa interacting protein 5, GMNN, and CDK2 were DE gene with statistical significance. For TP53, 15 genes were DE with statistical significance. Transcriptional misregulation in cancer was the frequently affected pathway. The CB-GEM bodies are effective highly conserved, splicesomal organelles that are needed for proper mRNA assembly. Certain mRNA of proteins of the CB-GEM bodies is influenced by TP53 status, gender, and tobacco use. Conclusion: The DE of CB-GEM bodies related protein in HNSCC patients are presented. Furthermore, we identified certain critical pathways, where the DE genes of CB-GEM bodies exert critical influence on HNSCC characteristics. This could potentially alter the HNSCC progression, treatment response, and prognosis.

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Section: Discussionmentioning

confidence: 99%

Study on mRNA expression of Cajal body – Gemini of coiled body proteins in head and neck squamous cell carcinoma

Thavarajah

Imaneul

Joshua

et al. 2020

IJMIO

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“…Accordingly, Gemin5 acts as a hub for several networks performing diverse key cellular functions. This multifunctional protein has been shown to act as a regulator of translation (Pacheco et al, 2009; Workman et al, 2015; Francisco-Velilla et al, 2018), as a ribosome-interacting protein (Francisco-Velilla 2016; Simsek et al, 2017), as a reprogramming factor in zebrafish lateral line hair cells (Pei et al, 2020), as a signal recognition particle (SRP)-interacting protein (Piazzon et al, 2013), and as a trans-splicing factor (Philippe et al, 2017). In addition, Gemin5 has been identified as a member of RNP networks associated to distinct cytoplasmic aggregates (Wollen et al, 2021; Vu et al, 2021; Jiang et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Functional and structural deficiencies of Gemin5 variants associated with neurological disease

Francisco‐Velilla

Embarc-Buh

Caño-Ochoa

et al. 2022

Preprint

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Dysfunction of RNA-binding proteins are often linked to a wide range of human disease in general, and particularly with neurological conditions. Gemin5 is a member of the survival of motor neuron (SMN) complex, a ribosome-binding protein and a translation reprogramming factor. Recently, pathogenic mutations in Gemin5 protein have been reported but the functional consequences of these variants remain elusive. Here we report functional and structural deficiencies associated with compound heterozygosity variants within the Gemin5 gene found in patients with neurodevelopmental disorders. These clinical variants are located in key domains of Gemin5, the tetratricopeptide repeat (TPR)-like dimerization module and the non-canonical RNA-binding site 1 (RBS1). We show that the TPR-like variants disrupt protein dimerization while the RBS1 variant confers protein instability. All mutants are defective in the interaction with protein networks involved in translation and RNA-driven pathways. Importantly, the TPR-like variants fail to associate with native ribosomes, abolishing the cap-dependent and selective translation control of Gemin5, and establishing a functional difference with the wild type protein. Our study provides a molecular basis of disease associated with malfunction of Gemin5 protein.

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A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation

Cited by 2 publications

References 64 publications

Study on mRNA expression of Cajal body – Gemini of coiled body proteins in head and neck squamous cell carcinoma

Study on mRNA expression of Cajal body – Gemini of coiled body proteins in head and neck squamous cell carcinoma

Functional and structural deficiencies of Gemin5 variants associated with neurological disease

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