• Title/Summary/Keyword: Post-transcriptional regulation

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The Existence of a Putative Regulatory Element in 3'-Untranslated Region of Proto-oncogene HOX11's mRNA

  • Li, Yue;Jiang, Zhao-Zhao;Chen, Hai-Xu;Leung, Wai-Keung;Sung, Joseph J.Y.;Ma, Wei-Jun
    • BMB Reports
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    • v.38 no.4
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    • pp.500-506
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    • 2005
  • HOX11 encodes a homeodomain-containing transcription factor which directs the development of the spleen during embryogenesis. While HOX11 expression is normally silenced through an unknown mechanism in all tissues by adulthood, the deregulation of HOX11 expression is associated with leukemia, such as T-cell acute lymphoblastic leukemia. The elucidation of regulatory elements contributing to the molecular mechanism underlying the regulation of HOX11 gene expression is of great importance. Previous reports of HOX11 regulatory elements mainly focused on the 5'-flanking region of HOX11 on the chromosome related to transcriptional control. To expand the search of putative cis-elements involved in HOX11 regulation at the post-transcriptional level, we analyzed HOX11 mRNA 3'-untranslated region (3'UTR) and found an AU-rich region. To characterize this AU-rich region, in vitro analysis of HOX11 mRNA 3'UTR was performed with human RNA-binding protein HuR, which interacts with AU-rich element (ARE) existing in the 3'UTR of many growth factors' and cytokines' mRNAs. Our results showed that the HOX11 mRNA 3'UTR can specifically bind with human HuR protein in vitro. This specific binding could be competed effectively by typical ARE containing RNA. After the deletion of the AU-rich region present in the HOX11 mRNA 3'UTR, the interaction of HOX11 mRNA 3'UTR with HuR protein was abolished. These findings suggest that HOX11 mRNA 3'UTR contains cis-acting element which shares similarity in the action pattern with RE-HuR interactions and may involve in the post-transcriptional regulation of the HOX11 gene.

Effects of Proto-oncogene Protein DEK on PCAF Localization

  • Lee, In-Seon;Lee, Seok-Cheol;Lee, Jae-Hwi;Seo, Sang-Beom
    • Biomolecules & Therapeutics
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    • v.15 no.2
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    • pp.78-82
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    • 2007
  • The proto-oncogene protein DEK is a nuclear binding phosphoprotein that has been associated with various human diseases including leukemia. Histone acetylation is an important post-translational modification which plays important role in transcriptional regulation. Auto-acetylation of histone acetyltransferase PCAF results in increment of its HAT activity and facilitation of its nuclear localization. In this study, we report that DEK inhibits PCAF auto-acetylation through direct interaction. The C-terminal acidic domains of DEK are responsible for the interaction with PCAF. Using confocal microscopy, we have shown that nuclear localization of PCAF is severely inhibited by DEK. Taken together, our results suggest that DEK may be involved in various cellular signal transduction pathways accommodated by PCAF through the regulation of PCAF auto-acetylation.

RNA-Protein Interactions and Protein-Protein Interactions during Regulation of Eukaryotic Gene Expression

  • Varani, Luca;Ramos, Andres;Cole, Pual T.;Neuhaus, David;Varani, Gabriele
    • Journal of the Korean Magnetic Resonance Society
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    • v.2 no.2
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    • pp.152-157
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    • 1998
  • The diversity of RNA functions ranges from storage and propagation of genetic information to enzymatic activity during RNA processing and protein synthesis. This diversity of functions requires an equally diverse arrays of structures, and, very often, the formation of functional RNA-protein complexes. Recognition of specific RNA signals by RNA-binding proteins is central to all aspects of post-transcriptional regulation of gene expression. We will describe how NMR is being used to understand at the atomic level how these important biological processes occur.

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Selection of Putative Iron-responsive Elements by Iron Regulatory Protein-2

  • Kim, Hae-Yeong
    • Journal of Applied Biological Chemistry
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    • v.42 no.2
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    • pp.62-65
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    • 1999
  • Iron regulatory proteins (IRPs) 1 and 2 bind with equally high affinity to specific RNA stem-loop sequences known as iron-responsive elements (IRE) which mediate the post-transcriptional regulation of many genes of iron metabolism. To study putative IRE-like sequences in RNA transcripts using the IRP-IRE interaction, Eight known genes from database were selected and the RNA binding activity of IRE-like sequences were compared to IRP-2. Among them, the IRE-like sequence in 3'-untranslational region (UTR) of divalent ration transporter-1 (DCT-1) shows a significant RNA binding affinity. This finding predicts that IRE consensus sequence present within 3'-UTR of DCT-1 might confer the regulation by IRP-2.

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Frequent Changes of 3' UTR Sequences in the Genes Expressed During Hematopoietic Differentiation Implicates the Importance of 3' UTR in Regulation of Gene Function (조혈세포의 분화과정에서 발현되는 유전자의 3‘ UTR 염기서열의 변화가 유전자 기능의 조절에 미치는 영향에 대한 연구)

  • Lee Sanggyu
    • YAKHAK HOEJI
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    • v.49 no.3
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    • pp.205-211
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    • 2005
  • The 3' UTR (3' untranslated region) plays important roles in controlling gene expression through regulating 3' polyadenylation, mRNA export, subcellular localization, translational efficiency, and mRNA stability. Changes in the 3' UTR sequence in an expressed transcript can result in functional changes of the genes that are expressed in pathological conditions compared with those genes expressed in normal physiologic conditions. A genome-wide survey of 3' UTR variation was performed for the genes expressed during hematopoietic differentiation from CD34+ stem/progenitor cells to CD 15 + myeloid progenitor cells. Wide-spread differential usage of the 3' UTR was observed from the genes expressed during this cellular transition. This study implies that the 3' UTR can be a highly coordinated region for post-transcriptional regulation of the function of expressed genes.

In vivo action of RNA G-quadruplex in phloem development

  • Cho, Hyunwoo;Cho, Hyun Seob;Hwang, Ildoo
    • BMB Reports
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    • v.51 no.11
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    • pp.547-548
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    • 2018
  • Phloem network integrates cellular energy status into post-embryonic growth, and development by tight regulation of carbon allocation. Phloem development involves complicated coordination of cell fate determination, cell division, and terminal differentiation into sieve elements (SEs), functional conduit. All of these processes must be tightly coordinated, for optimization of systemic connection between source supplies and sink demands throughout plant life cycle, that has substantial impact on crop productivity. Despite its pivotal role, surprisingly, regulatory mechanisms underlying phloem development have just begun to be explored, and we recently identified a novel translational regulatory network involving RNA G-quadruplex and a zinc-finger protein, JULGI, for phloem development. From this perspective, we further discuss the role of RNA G-quadruplex on post-transcriptional control of phloem regulators, as a potential interface integrating spatial information for asymmetric cell division, and phloem development.

Altered Translational Control of Fragile X Mental Retardation Protein on Myelin Proteins in Neuropsychiatric Disorders

  • Jeon, Se Jin;Ryu, Jong Hoon;Bahn, Geon Ho
    • Biomolecules & Therapeutics
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    • v.25 no.3
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    • pp.231-238
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    • 2017
  • Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ. Therefore, many research interests have been focused to identify RNA binding proteins and their regulatory mechanism in myelinating compartments. Fragile X mental retardation protein (FMRP) is one such RNA binding protein, regulating its target expression by translational control. Although the majority of works on FMRP have been performed in neurons, it is also found in the developing or mature glial cells including oligodendrocytes, where its function is not well understood. Here, we will review evidences suggesting abnormal translational regulation of myelin proteins with accompanying white matter problem and neurological deficits in fragile X syndrome, which can have wider mechanistic and pathological implication in many other neurological and psychiatric disorders.

Identification of Sperm mRNA Biomarkers Associated with Sex-Determination in Korean Native Cows

  • Min, Kwan-Sik;Byambaragchaa, Munkhzaya;Kim, Hyun;Park, Myung-Hum
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.2
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    • pp.111-116
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    • 2019
  • This study was conducted to analyze the specific genes associated with sex-determination in Korean native cow. The highly organized spermatogenesis requires accurate spatial and temporal regulation of gene expression, which is governed by transcriptional, post-transcriptional, and epigenetic processes. Recently, farmers have been interested in determining the sexual identity of the calves in their farm. We analyzed the sperm of Korean native and Holstein cows, which were supplied from Hanwoo Improvement Center. We evaluated sperm motility and expression of sperm-specific genes after treating semen with both male- and female reagents. Sperm motility in Korean native cows decreased by approximately 10% in the first 30 minutes after treatment with sex-determination reagent. However, sperm motility of Holstein cows decreased to 60-70% after 15 minutes and to 20-30% after 30 minutes. We selected six specific genes expressing in the spermatozoa to analysis the gene expression level. The Real-time PCR results suggest that the selected genes (Gimap4, Tmeff1, Rac2, Abi2, Rac1, and Clu) were highly expressed in the group treated with the male reagent compared to the group treated the female reagent and to the untreated-group (control). In the present study, we suggest that the selected genes play a pivotal role in sex-determination.

New Hairpin RNAi Vector with Brassica rapa ssp. pekinensis Intron for Gene Silencing in Plants

  • Lee, Gi-Ho;Lee, Gang-Seob;Park, Young-Doo
    • Horticultural Science & Technology
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    • v.35 no.3
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    • pp.323-332
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    • 2017
  • Homology-specific transcriptional and post-transcriptional silencing, an intrinsic mechanism of gene regulation in most eukaryotes, can be induced by anti-sense, co-suppression, or hairpin-based double-stranded RNA. Hairpin-based RNA interference (RNAi) has been applied to analyze gene function and genetically modify crops. However, RNAi vector construction usually requires high-cost cloning steps and large amounts of time, or involves methods that are protected by intellectual property rights. We describe a more effective method for generating intron-spliced RNAi constructs. To produce intron-spliced hairpin RNA, an RNAi cassette was ligated with the first intron and splicing sequences of the Brassica rapa ssp. pekinensis histone deacetylase 1 gene. This method requires a single ligation of the PCR-amplified target gene to SpeI-NcoI and SacI-BglII enzyme sites to create a gene-specific silencing construct. We named the resulting binary vector system pKHi and verified its functionality by constructing a vector to silence DIHYDROFLAVONOL 4-REDUCTASE (DFR), transforming it into tobacco plants, and confirming DFR gene-silencing via PCR, RT-qPCR, and analysis of the accumulation of small interfering RNAs. Reduction of anthocyanin biosynthesis was also confirmed by analyzing flower color of the transgenic tobacco plants. This study demonstrates that small interfering RNAs generated through the pKHi vector system can efficiently silence target genes and could be used in developing genetically modified crops.

Characterization of transcription factor genes related to cold tolerance in Brassica napus

  • Sharma, Mayur Mukut Murlidhar;Ramekar, Rahul Vasudeo;Park, Nam-Il;Choi, Ik-Young;Choi, Seon-Kang;Park, Kyong-Cheul
    • Genomics & Informatics
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    • v.19 no.4
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    • pp.45.1-45.8
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    • 2021
  • Brassica napus is the third most important oilseed crop in the world; however, in Korea, it is greatly affected by cold stress, limiting seed growth and production. Plants have developed specific stress responses that are generally divided into three categories: cold-stress signaling, transcriptional/post-transcriptional regulation, and stress-response mechanisms. Large numbers of functional and regulatory proteins are involved in these processes when triggered by cold stress. Here, our objective was to investigate the different genetic factors involved in the cold-stress responses of B. napus. Consequently, we treated the Korean B. napus cultivar Naehan at the 4-week stage in cold chambers under different conditions, and RNA and cDNA were obtained. An in silico analysis included 80 cold-responsive genes downloaded from the National Center for Biotechnology Information (NCBI) database. Expression levels were assessed by reverse transcription polymerase chain reaction, and 14 cold-triggered genes were identified under cold-stress conditions. The most significant genes encoded zinc-finger proteins (33.7%), followed by MYB transcription factors (7.5%). In the future, we will select genes appropriate for improving the cold tolerance of B. napus.