• Journal of Life Science
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• v.19 no.4
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• pp.549-552
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• 2009

Genetic mutations by gene fusion result from chromosomal rearrangement, trans-splicing, and intergenic splicing. Trans-splicing is a phenomenon in which two pre-mRNAs grow together into one. We analyzed the trans-splicing products in embryonic stem cells. By using bioinformatic tools, 70 trans-splicing transcripts were identified. They are classified into 6 types according to fusion pattern: 5'UTR-5'UTR, 5'UTR-3'UTR, 3'UTR-3'UTR, 5'UTR-CDS, 3'UTR-CDS, CDS-CDS. The fusion products are more abundant in CDS regions than in UTR regions, which contain multiple intron numbers. Chromosome analysis showing gene fusion via trans-splicing indicated that chromosomes 17 and 19 were activated. These data are of great use for further studies in relation to fusion genes and human diseases.

• Molecules and Cells
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• v.37 no.9
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• pp.644-649
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• 2014

The 3' ends of most eukaryotic messenger RNAs must undergo a maturation step that includes an endonuc-leolytic cleavage followed by addition of a polyadenylate tail. While this reaction is catalyzed by the action of only two enzymes it is supported by an unexpectedly large number of proteins. This complexity reflects the necessity of coordinating this process with other nuclear events, and growing evidence indicates that even more factors than previously thought are necessary to connect 3' processing to additional cellular pathways. In this review we summarize the current understanding of the molecular machinery involved in this step of mRNA maturation, focusing on new core and auxiliary proteins that connect polyadenylation to splicing, DNA damage, transcription and cancer.

• Journal of Microbiology
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• v.33 no.3
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• pp.201-207
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• 1995

We have previously reported that SPP2 gene product of yeast Saccharomyces cerevisiae is involved in the pre-mRNA splicing. To investigate the rol ein the splicing pathway of the Spp2p protein, the SPP2 gene was overexpressed in Escherichia coli and polyclonal antibodies to Spp2p were generated from rabbits. First, a DNA fragment containing the SPP2 GENE without its promoter was subcloned into an E. coli expression vector, pKK233-3. The resulting recombinant plasmid pBQ14 contained an IPTG inducible tac promoter and the SPP2 structural gene. Overexpression of the SPP2 gene was achieved by additionof 0.1 to 1.0 mM IPTG to a logarithmic culture of E. coli JM103(pBQ14) for 90 min at 37.deg.C. Sequence of N-terminal 15 amino acids of the overproduced protein was well matched to the deduced one from the SPP2 reading frame. Then, polyclonal antibodies were generated from rabbits immunized with gel-purified SppSp protein. These antibodies reacted specifically with the Spp2p protein extracted from yeast cells expressing the SPP2 gene to a great extent. The antibodies could also block the activity of yeast splicing extracts.

• Proceedings of the Zoological Society Korea Conference
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• 2003.08a
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• pp.166.3-166
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• 2003

No Abstract, See Full Text

• The Journal of Korean Physical Therapy
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• v.13 no.2
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• pp.433-444
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• 2001

This review highlights the ontogenesis and the differentiation of motor neuron in spinal cord, and introduce the survival motor neuron(SMN) which is associated with growth and survival of motor neurons. The differentiation of floor plate cells and motor neurons in the vertebrate neural tube appears to be induced by signals from the notochord. This signal is Sonic hedgehog(Shh). The early development of motor neurons involves the inductive action of Shh. The SMN gene is essential for embryonic viability. SMN mRNA is also expressed in virtually all cell types in spinal cord, including large motor neurons. The SMN protein is involved in RNA processing and during early embryonic development is necessary fer cell survival. Two SMN genes are present in 5q 13 in humans: the telomeric gene(SMNt), which is the SMA-determining gene, and the centromeric analog gene(SMNc). The majority of transcripts from the SMNt gene are full length but, major transcripts of the SMNc gene have a high degrees of alternative splicing and tend to have little or no exon 7. The SMN is involved in the RNA processing(the biogenesis of snRNPs and pre-mRNA splicing), the anti-apoptotic effects, and regulating gene expression.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.1-8
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• 2005

Myotonic Dystrophies type 1 and 2 (DM1/2) are neuromuscular disorders which belong to a group of genetic diseases caused by unstable CTG triplet repeat (DM1) and CCTG tetranucleotide repeat (DM2) expansions. In DM1, CTG repeats are located within the 3' untranslated region of myotonin protein kinase (DMPK) gene on chromosome 19q. DM2 is caused by expansion of CCTG repeats located in the first intron of a gene coding for zinc finger factor 9 on chromosome 3q. The CTG and CCTG expansions are located in untranslated regions and are expressed as pre-mRNAs in nuclei (DM1 and DM2) and as mRNA in cytoplasm (DM1). Investigations of molecular alterations in DM1 discovered a new molecular mechanism responsible for this disease. Expansion of un-translated CUG repeats in the mutant DMPK mRNA disrupts biological functions of two CUG-binding proteins, CUGBP and MNBL. These proteins regulate translation and splicing of mRNAs coding for proteins which play a key role in skeletal muscle function. Expansion of CUG repeats alters these two stages of RNA metabolism in DM1 by titrating CUGBP1 and MNBL into mutant DMPK mRNA-protein complexes. Mouse models, in which levels of CUGBP1 and MNBL were modulated to mimic DM1, showed several symptoms of DM1 disease including muscular dystrophy, cataracts and myotonia. Mis-regulated levels of CUGBP1 in newborn mice cause a delay of muscle development mimicking muscle symptoms of congenital form of DM1 disease. Since expansion of CCTG repeats in DM2 is also located in untranslated region, it is predicted that DM2 mechanisms might be similar to those observed in DM1. However, differences in clinical phenotypes of DM1 and DM2 suggest some specific features in molecular pathways in both diseases. Recent publications suggest that number of pathways affected by RNA CUG and CCUG repeats could be larger than initially thought. Detailed studies of these pathways will help in developing therapy for patients affected with DM1 and DM2.

• Molecules and Cells
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• v.43 no.7
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• pp.662-670
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• 2020

We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

• The Korean Journal of Food & Health Convergence
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• v.4 no.4
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• pp.18-25
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• 2018

Proteins play a key role in many functions such as metabolic activity, differentiation, as cargos and cell fate regulators. It is necessary to know about the markers involved in male fertility in order to develop remedies for the treatment of male infertility. But, the role of the proteins is not limited to particular function in the biological systems. Some of the proteins act as ion channels such as catsper and proteins like Nanos acts as a translational repressor in germ cells and expressed in prenatal period whose role in male fertility is uncertain. Rbm5 is a pre mRNA splicing factor necessary for sperm differentiation whose loss of function results deficit in sperm production. DEFB114 is a beta defensin family protein necessary for sperm motility in LPS challenged mice where as TEX 101 is a plasma membrane specific germ cell protein whose function is not clearly known u to now. Gpr56 is another adhesion protein whose null mutation leads to arrest of production of pups in rats. Amyloid precursor protein role in Alzheimer's disease is already known but it plays an important role in male fertility also but its function is uncertain and has to be considered while targeting APP during the treatment of Alzheimer's disease. The study on amyloid precursor protein in male fertility is a novel thing but requires further study in correlation to alzheimer's disease.

• Molecules and Cells
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• v.39 no.7
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• pp.573-579
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• 2016

During copulation, male Drosophila transfers Sex Peptide (SP) to females where it acts on internal sensory neurons expressing pickpocket (ppk). These neurons induce a post-mating response (PMR) that includes elevated egg-laying and refractoriness to re-mating. Exactly how ppk neurons regulate the different aspects of the PMR, however, remains unclear. Here, we identify a small subset of the ppk neurons which requires expression of a pre-mRNA splicing factor CG3542 for egg-laying, but not refractoriness to mating. We identify two CG3542-ppk expressing neurons that innervate the upper oviduct and appear to be responsible for normal egg-laying. Our results suggest specific subsets of the ppk neurons are responsible for each PMR component.

• BMB Reports
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• v.56 no.11
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• pp.612-617
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• 2023

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.