Abstract
Coilin is the main component of Cajal body (CB), a membraneless organelle that is involved in the biogenesis of ribonucleoproteins and telomerase, cell cycle, and cell growth. The disruption of CBs is linked to neurodegenerative diseases and potentially cancers. The coilin gene (COIL) contains two nonsynonymous SNPs: rs116022828 (E121K) and rs61731978 (V145I). Here, we investigated for the first time the functional impacts of these coilin SNPs on CB formation, coilin subcellular localization, microtubule formation, cell growth, and coilin expression and protein structure. We revealed that both E121K and V145I mutants could disrupt CB formation and result in various patterns of subcellular localization with survival motor neuron protein. Noteworthy, many of the E121K cells showed nucleolar coilin accumulation. The microtubule regrowth and cell cycle assays indicated that the E121K cells appeared to be trapped in the S and G2/M phases of cell cycle, resulting in reduced cell proliferation. In silico protein structure prediction suggested that the E121K mutation caused greater destabilization on the coilin structure than the V145I mutation. Additionally, clinical bioinformatic analysis indicated that coilin expression levels could be a risk factor for cancer, depending on the cancer types and races.
Highlights
Cajal body (CB), a membraneless subnuclear organelle, is essential for the assembly and modification of small nuclear ribonucleoproteins, small nucleolar ribonucleoproteins, and telomerase [1]
The coilin gene (COIL) gene in the HeLa cells was sequenced to check for mutations, and the results indicated that the cells contained coilin WT
Studies have identified a range of proteins that localized to the CBs and, among them, coilin is widely recognized as the main component of, and a molecular marker for, CBs [2,5,39]
Summary
Cajal body (CB), a membraneless subnuclear organelle, is essential for the assembly and modification of small nuclear ribonucleoproteins (snRNPs), small nucleolar ribonucleoproteins (snoRNPs), and telomerase [1]. CBs or CB-like structures can be found in many living organisms, including human, mammalian, plant, yeast, amphibian, and insect [2,3]. CBs are not necessarily observable in all cell types, but more commonly in those that are transcriptionally active and/or with high splicing demands, such as neuronal and cancerous cells [4,5]. CBs, the number and size of CBs could change according to their proliferative and metabolic status, indicating the involvement of CBs in cell growth [6,7,8]. The CB consists of several important components, including coilin and survival motor neuron (SMN) protein [9]. The human coilin is encoded by the gene COIL (HGNC: 2184), and it is considered as the architectural element and marker protein of the CBs. Structural studies of coilin have revealed
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