• Molecules and Cells
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• v.41 no.9
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• pp.818-829
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• 2018

Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying amyotrophic lateral sclerosis (ALS), which may in turn pinpoint potential therapeutic targets for treatment. The ALS research field has evolved with recent discoveries of numerous genetic mutations in ALS patients, many of which are in genes encoding RNA binding proteins (RBPs), including TDP-43, FUS, ATXN2, TAF15, EWSR1, hnRNPA1, hnRNPA2/B1, MATR3 and TIA1. Accumulating evidence from studies on these ALS-linked RBPs suggests that dysregulation of RNA metabolism, cytoplasmic mislocalization of RBPs, dysfunction in stress granule dynamics of RBPs and increased propensity of mutant RBPs to aggregate may lead to ALS pathogenesis. Here, we review current knowledge of the biological function of these RBPs and the contributions of ALS-linked mutations to disease pathogenesis.

• Journal of Plant Biology
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• v.39 no.4
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• pp.279-286
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• 1996

To know the changes of rbcL mRNA level by illumination, Northern hybridization analysis was performed with maize (Zea mays L.cv. Golden X Bantam). The average level of rbcL. mRNA in the light-grown shoots was 3.1 times higher than that of the dark-grown shoots after 6 to 10 growth days. The maximum difference of rbcL mRNA level between the dark-grown and the light-grown shoots was 5.1 folds. These results indicate that accumulation of rbcL mRNAin maize shoots is induced by light. Since the transcriptional DNA binding proteins and their cognate promoter elements, we carried out gel-retardation assays to elucidate the specific binding proteins on the rbcL promoter. It was found that plastid proteins of light-grown shoots bound to the R2 DNA fragment (-33 to -229) and R3 DNA fragment (-230 to -418 from ATG) of the rbcL promoter. From the results of competitive binding assays and heat or protease treatments, it was demonstrated that the bindings were sequence-specific DNA-protein interactions. Therefore, it could be concluded that the rbcL promoter region has at least two specific recognition sites for plastid proteins.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.180-180
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• 1996

Previous studies have shown that kainic acid (KA) causes an elevation of hippocampal proenkephalin mRNA level. However, the role of proto-oncogene products, such as c-Fos, c-Jun and Fra proteins in the regulation of KA-induced proenkephalin mRNA increase in the hippocampus has not been well characterized. Thus, in the present study, the effect of cycloheximide (CHX) on KA-induced proenkephalin mRNA and immediate early gene products induction was examined. After pretreating with either vehicle or CHX (20 mg/kg, s.c.) for 30 min, KA (10 mg/kg) was administered s.c. The animals were sacrificed 1,2, or 8 hrs after KA administration. Total RNA and were isolated for Northern blot assay, and proteins were isolated for Western and electrophoretic gel-shift assays. First, we found that CHX inhibited KA-induced proenkephalin mRNA increase without altering intracellular proenkephalin protein level. Secondly, Western blot assays showed that KA increased c-Fos, c-Jun and Fra proteins at 1,2, and 8 hrs and CHX inhibited these immediate early gene products. Finally, electrophoretic gel shift assays revealed that KA increased both AP-1 and ENKCRE-2 DNA binding activities. Furthermore, CHX attenuated KA-induced AP-1 and ENKCRE-2 DNA binding activities. Both AP-1 and ENKCRE-2 DNA binding activities were abolished by cold AP-1 or ENKCRE-2 oligonucleotides, and further reduced by antibodies against c-Fos or c-Jun. Antibody against CREB reduced ENKCRE-2, but not AP-1, DNA binding activity. Our results suggest that on-going protein synthesis is required for elevation of hippocampal proenkephalin mRNA level induced by KA. All c-Fos, c-Jun, and Fra proteins appears to be involved in the regulation of hippocampal proenkephalin mRNA level induced by KA (This study was supported by a grant from KOSEF).

• BMB Reports
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• v.44 no.3
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• pp.147-157
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• 2011

The meiotic process from the primordial stage to zygote in female germ cells is mainly adjusted by post-transcriptional regulation of pre-existing maternal mRNA and post-translational modification of proteins. Several key proteins such as the cell cycle regulator, Cdk1/cyclin B, are post-translationally modified for precise control of meiotic progression. The second messenger (cAMP), kinases (PKA, Akt, MAPK, Aurora A, CaMK II, etc), phosphatases (Cdc25, Cdc14), and other proteins (G-protein coupled receptor, phosphodiesterase) are directly or indirectly involved in this process. Many proteins, such as CPEB, maskin, eIF4E, eIF4G, 4E-BP, and 4E-T, post-transcriptionally regulate mRNA via binding to the cap structure at the 5' end of mRNA or its 3' untranslated region (UTR) to generate a closed-loop structure. The 3' UTR of the transcript is also implicated in post-transcriptional regulation through an association with proteins such as CPEB, CPSF, GLD-2, PARN, and Dazl to modulate poly(A) tail length. RNA interfering is a new regulatory mechanism of the amount of mRNA in the mouse oocyte. This review summarizes information about post-transcriptional and post-translational regulation during mouse oocyte meiotic maturation.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.3051-3056
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• 2011

We calculate the free energy surfaces for two small proteins and a protein-RNA complex system by using a lattice model approach. In particular, we employ the Munoz-Eaton model, which is a native-structure based statistical mechanical model for studying protein folding problem. The model can provide very useful insights into the folding mechanisms by allowing one to calculate the free energy surfaces efficiently. We first calculate the free energy surfaces of ubiquitin and BBL, using both approximate and recently developed exact solutions of the model. Ubiquitin exhibits a typical two-state folding behavior, while BBL downhill folding in our study. We then extend the method to study of a protein-RNA complex. In particular, we focus on PAZ-siRNA complex. In order to elucidate the interplay between folding and binding kinetics for this system we perform comparative studies of PAZ only, PAZ-siRNA complex and two mutated complexes. We find that folding and binding are strongly coupled with each other and the bound PAZ is more stable than the unbound PAZ. Our results also suggest that the binding sites of the siRNA may serve act as a nucleus in the folding process.

• BMB Reports
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• v.32 no.1
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• pp.82-85
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• 1999

The movement protein of cucumber mosaic virus (CMV) is required for cell-to-cell movement of viral RNA. The movement of viral RNA occurs through the plant intercellular connection, the plasmodesmata. The viral movement protein was known to be multi-functional. In this work, a series of deletion mutants of CMV movement protein gene were created to identify the functional domains. The mutated movement proteins were produced as inclusion body in E. coli, and purified and renatured. A polyclonal antibody was raised against the CMV-Kor strain (Korean isolate) movement protein expressed in E. coli. The ability of the truncated proteins to bind to ssRNA was assayed by UV cross-linking and gel retardation analyses. The results indicate that the domain between amino acids 118 and 160 of CMV movement protein is essential for ssRNA binding.

• BMB Reports
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• v.43 no.1
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• pp.1-8
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• 2010

The cold shock domain (CSD) is among the most ancient and well conserved nucleic acid binding domains from bacteria to higher animals and plants. The CSD facilitates binding to RNA, ssDNA and dsDNA and most functions attributed to cold shock domain proteins are mediated by this nucleic acid binding activity. In prokaryotes, cold shock domain proteins only contain a single CSD and are termed cold shock proteins (Csps). In animal model systems, various auxiliary domains are present in addition to the CSD and are commonly named Y-box proteins. Similar to animal CSPs, plant CSPs contain auxiliary C-terminal domains in addition to their N-terminal CSD. Cold shock domain proteins have been shown to play important roles in development and stress adaptation in wide variety of organisms. In this review, the structure, function and regulation of plant CSPs are compared and contrasted to the characteristics of bacterial and animal CSPs.

• Genomics & Informatics
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• v.17 no.4
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• pp.36.1-36.6
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• 2019

The incidence and mortality rate of cancer continues to gradually increase, although considerable research effort has been directed at elucidating the molecular mechanisms underlying biomarkers responsible for tumorigenesis. Accumulated evidence indicates that the long non-coding RNAs (lncRNAs), which are transcribed but not translated into functional proteins, contribute to cancer development. Recently, linc00152 (an lncRNA) was identified as a potent oncogene in various cancer types, and shown to be involved in cancer cell proliferation, invasiveness, and motility by sponging tumor-suppressive microRNAs acting as a competing endogenous RNA, binding to gene promoters acting as a transcriptional regulator, and binding to functional proteins. In this review, we focus on the oncogenic role of linc00152 in tumorigenesis and provided an overview of recent clinical studies on the effects of linc00152 expression in human cancers.

• BMB Reports
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• v.50 no.4
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• pp.194-200
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• 2017

Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3'-untranslated regions (UTRs) of mRNAs. mRNA 3'-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay. Each RNA binding protein that binds to these cis-acting elements regulates mRNA translation via various mechanisms targeting the mRNA cap structure, the eukaryotic initiation factor 4E (eIF4E)-eIF4G complex, ribosomes, and the poly (A) tail. We also discuss translation-mediated regulation of mRNA fate.

• Journal of Life Science
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• v.25 no.10
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• pp.1184-1195
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• 2015

The zebrafish is an emerging vertebrate model organism in reproductive biology. The oocyte maturation of zebrafish is triggered by maturation inducing hormone (MIH, 17α,20β-Dihydroxy-4-pregnen-3-one). In almost all animals, the oocyte maturation is governed by activation of pre-MPF which consists of cyclinB and inactive Cdk1. In the oocyte of Xenopus and mice, the activity of Cdk1 is regulated in two ways, one is the interaction with cyclinB and the other is phosphorylation/dephosphorylation of T14/Y15 residues on the Cdk1 by Wee1 and Cdc25. Unlike Xenopus and mice that have a sufficient amount of pre-MPF, pre-MPF is absent in GV oocyte of most teleost including zebrafish. Therefore, the activation of MPF during zebrafish oocyte maturation might totally depend on de novo synthesis of cyclinB proteins. It is reported that the translation of maternal mRNA is regulated by combination of several RNA binding proteins such as CPEB, Dazl, Pum1/Pum2, and insulin-like growth factor2 mRNA-binding protein 3 in the zebrafish oocytes. However, the definitive mechanism of these proteins to regulate the translation of stored maternal mRNAs remains to be elucidated. Therefore, the investigation of the maturation process of the zebrafish oocyte will provide new information that can help identify the role of translational control in early vertebrate oocyte maturation.