• BMB Reports
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• 제38권4호
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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.

• Clinical and Experimental Pediatrics
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• 제46권4호
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• pp.335-339
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• 2003

목 적 : 폐 표면 활성제 단백질-A는 폐 표면 활성제의 생리작용과 구조에 관여하며, 폐의 숙주방어와 염증반응에 주된 역할을 하고 있다. 스테로이드 치료는 미숙아의 분만이 예측되는 산모에 대해서 미숙아의 급성 호흡곤란 증후군 등을 예방할 목적으로, 또는 미숙아의 만성 폐질환을 예방하기 위하여 널리 사용되고 있다. 현재까지 인간에서 두 가지의 SP-A 유전자 및 여러 종류의 대립형질이 밝혀져 있고, 덱사메타손 치료에 서로 다른 반응을 보이고 있으며, SP-A 3'UTR이 관여 할 가능성이 있다는 연구가 발표되었다. 저자들은 가장 많은 빈도를 보이는 8가지 SP-A 대립형질에서 덱사메타손 처치에 대하여 서로 다른 반응이 3'UTR에 의하여 이루어지는지를 규명하고자 연구를 하였다. 방 법 : 리포터 유전자로서 luciferase를 사용하여 8종류의 SP-A 대립형질의 3'UTR을 포함하는 구성체를 만들었다. 이 구성체들은 SV40 promotor에 의하여 조절되었으며, SP-A를 생산하는 H441 세포내로 형질도입 되었다. 덱사메타손 처치 후 리포터 유전자의 활성도를 측정하였으며, 대조군에 따라 표준화되었다. 결 과 : 덱사메타손 처치 시 $6A^3$, 6A, 1A 대립 유전자에서 리포터 유전자의 활성 반응이 유의하게 감소하였다. 결 론 : SP-A 유전자 변이 중 덱사메타손 처치에 대한 유전자 표현 반응이 서로 다르다는 사실은 스테로이드 치료 시 미숙아의 개개인의 SP-A 유전자 변이에 따라 고려하여 사용해야함이 타당할 것으로 생각된다.

• Genomics & Informatics
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• 제2권2호
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• pp.86-91
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• 2004

Even though it represents $6-13\%$ of human genomic DNA, Alu sequences are rarely found in coding regions. When in exon region, over $80\%$ of them are found in 3' untranslated region (UTR). Pseudogenes are an important component of human genome. Their functions are not clearly known and the mechanism of how they are generated is still debatable. Both the Alu and Pseudogenes are important research problems in molecular biology. mRNA is thought to be a prime source of pseudogene and active research is going on its molecular mechanism. We report, for the first time, that mRNAs containing Alu repeats at 3' UTR has a significantly high correlation with processed pseudogenes, suggesting a possibility that Alu containing mRNAs have a high tendency to become processed pseudogenes. It is known that about $10\%$ of all human genes have been transposed. Transposed genes at 3' UTR without Alu repeat have about two processed pseudogenes per gene on average while we found with statistical significance that a transposed gene with Alu had over three processed Pseudogenes on average. Therefore, we propose Alu repeats as a new and important factor in the generation of pseudogenes.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1923-1927
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• 2012

Background: Studies investigating the association between 2R/3R polymorphisms in the thymidylate synthase 5'-untranslated enhanced region (TYMS 5'-UTR) and gastric cancer risk have generated conflicting results. Thus, a meta-analysis was performed to summarize the data on any association. Methods: Pubmed, Embase, and CNKI databases were searched for all available studies. The strength of association between TYMS 5'-UTR 2R/3R polymorphism and gastric cancer risk was estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Results: Six individual case-control studies with a total of 1, 472 cases and 1, 895 controls were included into this meta-analysis. Analyses of total six relevant studies showed that there was no obvious association between the TYMS 5'-UTR 2R/3R polymorphism and gastric cancer risk. Subgroup analyses based on ethnicity showed 2R of TYMS 5'-UTR 2R/3R contributes to gastric cancer risk in the Asian population ($OR_{Homozygote\;model}$ = 1.71, 95%CI 1.19-2.46, P = 0.004; $OR_{Recessive\;genetic\;model}$ = 1.70, 95%CI 1.18-2.43, P = 0.004). However, the association in Caucasian populations was uncertain due to the limited studies. Conclusions: Our meta-analysis suggests that 2R of TYMS 5'-UTR 2R/3R contributes to gastric cancer risk in the Asian population, while this association in Caucasians populations needs further study.

• Molecules and Cells
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• 제39권4호
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• pp.281-285
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• 2016

Almost all of eukaryotic mRNAs are subjected to polyadenylation during mRNA processing. Recent discoveries showed that many of these mRNAs contain more than one polyadenylation sites in their 3' untranslated regions (UTR) and that alternative polyadenylation (APA) is prevalent among these genes. Many biological processes such as differentiation, proliferation, and tumorigenesis have been correlated to global APA events in the 3' UTR of mRNAs, suggesting that these APA events are tightly regulated and may play important physiological roles. In this review, recent discoveries in the physiological roles of APA events, as well as the known and proposed mechanisms are summarized. Perspective for future directions is also discussed.

• 한국수정란이식학회지
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• 제29권3호
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• pp.297-303
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• 2014

The objective of this study was to determine the breed differences in the 3'-untranslated region (UTR) of MC1R mRNA, which may be used to distinguish Korean brindle cattle (Chikso) from other breeds. We investigated the relationship between the variation of 3'-UTR of the MC1R mRNA and coat color among different breeds and the Korean brindle cattle with different coat colors. MC1R mRNA expression levels were determined in accordance with the coat color and hair colors of the tail. Total cellular RNA was extracted from the hair follicles of the tails in Hanwoo, Korean brindle cattle, Holstein and $Hanwoo{\times}Holstein$ crossbred cattle. After cDNA synthesis, PCR was performed. Sequences of the 3'-UTR of MC1R mRNA were analyzed. The 3'-UTR of the MC1R mRNA from different breeds of cattle did not show any variations. There were no variations in the 3'-UTR of the MC1R mRNA in Korean brindle cattle with different coat colors. The levels of MC1R mRNA expression in hair follicles of the tail varied substantially among the Korean brindle cattle with different coat colors, except yellow coat color. Correlation between the MC1R mRNA expression in the hair follicles of the tail and coat color may be present in the Korean brindle cattle, but not between the variations of 3'-UTR of MC1R mRNA and coat color. Further studies to determine the regulation of MC1R mRNA expression from the hair follicles of different coat colors will be beneficial in clarifying the role of MC1R in the coat colors of the Korean brindle cattle.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3971-3977
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• 2016

Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

• 생명과학회지
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• 제33권12호
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• pp.987-994
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• 2023

이 연구는 제주도 한우집단에서 galactose mutarotase (GALM) 유전자형과 도체형질의 연관성을 시험하였다. GALM 유전자형은 3'-비해독부위(3'-UTR)의 14-bp (5'-GGTCTAATGACCAG-3') 삽입/결실 다형성을 이용하였다. 한우 비육우 집단에서 GALM 유전자의 세 가지 유전자형(LL, LS, SS)이 모두 관찰되었다. 연관성 분석결과는 근내지방의 함량과 밀접한 상관을 보이는 육질등급과 근내지방도의 수준과, 등지방두께의 수준이 유전자형에 따른 유의적인 차이를 나타내었다(p<0.05). 동형접합인 SS 유전자형을 보유한 도체에서 LL 또는 LS 유전자형인 도체에 비해 근내지방 함량 수준은 더 높고, 등지방두께도 더 얇은 수준을 보였다. 반면, 도체중, 등심단면적, 육색, 지방색 등은 GALM 유전자형에 따른 유의적인 차이는 없었다(p>0.05). 3'-UTR에서 14-bp 절편의 결실은 RNA의 2차 구조의 변형과 RNA-결합 단백질, microRNA와의 결합능력에 대한 방해를 통해 유전자 발현에 영향을 줄 수 있는 것으로 예측되었다. GALM 유전자의 3'-UTR 영역에서 14-bp 삽입/결실 다형성에 대한 이번 연구결과는 소에서 근육과 등지방 조직에서 galactose 대사에 의한 지방 축적을 통해 성장형질, 도체형질에 영향을 주는 것으로 판단된다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권12호
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• pp.1679-1683
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• 2017

Objective: An experiment was conducted to study the association between the single nucleotide polymorphisms (SNPs) in 5'-untranslated regions (5'-UTR) of equine chorionic gonadotropin (eCG) genes and the serum eCG levels. Methods: SNPs in 5'-UTR of eCG genes were screened across 10 horse breeds, including 7 Chinese indigenous breeds and 3 imported breeds using iPLEX chemistry, and the association between the serum eCG levels of 174 pregnant Da'an mares and their serum eCG levels (determined with ELISA) was analyzed. Results: Four SNPs were identified in the 5'-UTR of the $eCG{\alpha}$ gene, and one of them was unique in the indigenous breeds. There were 2 SNPs detected at the 5' end of the $eCG{\beta}$ subunit gene, and one of them was only found in the Chinese breeds. The SNP g.39948246T>C at the 5'-UTR of $eCG{\alpha}$ was associated significantly with eCG levels of 75-day pregnant mare serum (p<0.05) in Da'an mares. Prediction analysis on binding sites of transcription factors showed that the g.39948246T>C mutation causes appearance of the specific binding site of hepatocyte nuclear factor 3 forkhead homolog 2 (HFH-2), which is a transcriptional repressor belonging to the forkhead protein family of transcription factors. Conclusion: The SNP g.39948246T>C at the 5'-UTR of $eCG{\alpha}$ is associated with eCG levels of 75-day pregnant mare serum (p<0.05).

• Animal Bioscience
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• 제34권5호
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• pp.801-810
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• 2021

Objective: microRNAs (miRNAs) can play a role in a variety of physiological and pathological processes, and their role is achieved by regulating the expression of target genes. Our previous high-throughput sequencing found that ssc-miR-185 plays an important regulatory role in piglet diarrhea, but its specific target genes and functions in intestinal porcine epithelial cell (IPEC-J2) are still unclear. We intended to verify the target relationship between porcine miR-185 and cell division cycle 42 (CDC42) gene in IPEC-J2 and to explore the effect of miR-185 on the proliferation of IPEC-J2 cells. Methods: The TargetScan, miRDB, and miRanda software were used to predict the target genes of porcine miR-185, and CDC42 was selected as a candidate target gene. The CDC42-3' UTR-wild type (WT) and CDC42-3'UTR-mutant type (MUT) segments were successfully cloned into pmirGLO luciferase vector, and the luciferase activity was detected after co-transfection with miR-185 mimics and pmirGLO-CDC42-3'UTR. The expression level of CDC42 was analyzed using quantitative polymerase chain reaction and Western blot. The proliferation of IPEC-J2 was detected using cell counting kit-8 (CCK-8), methylthiazolyldiphenyl-tetrazolium bromide (MTT), and 5-ethynyl-2'-deoxyuridine (EdU) assays. Results: Double enzyme digestion and sequencing confirmed that CDC42-3'UTR-WT and CDC42-3'UTR-MUT were successfully cloned into pmirGLO luciferase reporter vector, and the luciferase activity was significantly reduced after co-transfection with miR-185 mimics and CDC42-3'UTR-WT. Further we found that the mRNA and protein expression level of CDC42 were down-regulated after transfection with miR-185 mimics, while the opposite trend was observed after transfection with miR-185 inhibitor (p<0.01). In addition, the CCK-8, MTT, and EdU results demonstrated that miR-185 promotes IPEC-J2 cells proliferation by targeting CDC42. Conclusion: These findings indicate that porcine miR-185 can directly target CDC42 and promote the proliferation of IPEC-J2 cells. However, the detailed regulatory mechanism of miR-185/CDC42 axis in piglets' resistance to diarrhea is yet to be elucidated in further investigation.