• 제목/요약/키워드: alternative splicing

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SR Proteins: Binders, Regulators, and Connectors of RNA

  • Jeong, Sunjoo
    • Molecules and Cells
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    • 제40권1호
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    • pp.1-9
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    • 2017
  • Serine and arginine-rich (SR) proteins are RNA-binding proteins (RBPs) known as constitutive and alternative splicing regulators. As splicing is linked to transcriptional and post-transcriptional steps, SR proteins are implicated in the regulation of multiple aspects of the gene expression program. Recent global analyses of SR-RNA interaction maps have advanced our understanding of SR-regulated gene expression. Diverse SR proteins play partially overlapping but distinct roles in transcription-coupled splicing and mRNA processing in the nucleus. In addition, shuttling SR proteins act as adaptors for mRNA export and as regulators for translation in the cytoplasm. This mini-review will summarize the roles of SR proteins as RNA binders, regulators, and connectors from transcription in the nucleus to translation in the cytoplasm.

Induction of ER-stress by Heat Shock in the Thyrocytes

  • ;;양영모
    • 대한의생명과학회지
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    • 제12권4호
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    • pp.435-438
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    • 2006
  • In eukaryotes, ER stress induces UPR (unfolded protein response) via IRE1 activation which sends a molecular signal for XBP1 mRNA splicing in the cytosol. During this mRNA splicing, 23 nt removed in which contains PstI site and then resulting XBP1 product is not digested with PstI restriction enzyme. In this study, using this XBP1 mRNA splicing mechanism, the effect of heat shock on thyrocytes is studied, because heat shock response in the thyrocytes needs more study to understand thyroid physiology under alternative environments. ER inducible drugs (tunicamycin, DTT, $Ca^{2+}$ ionopore A23187, BFA) induce ER stress in the thyrocytes. From 3 hours after heat shock, ER stress is induced and which is reversible when heat shock is without. While $Ca^{2+}$ ionopore A23187 is reversible from ER stress by washing out the drug, thapsigagin is irreversible. Other ER inducible drugs are not so sensitive to ER stress repairing. XBP1 mRNA splicing in a cell is very available method to detect ER stress. It needs only a small quantity of total RNA and processing also very easy.

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Molecular Analysis of Alternative Transcripts of the Equine Cordon-Bleu WH2 Repeat Protein-Like 1 (COBLL1) Gene

  • Park, Jeong-Woong;Jang, Hyun-Jun;Shin, Sangsu;Cho, Hyun-Woo;Choi, Jae-Young;Kim, Nam-Young;Lee, Hak-Kyo;Do, Kyong-Tak;Song, Ki-Duk;Cho, Byung-Wook
    • Asian-Australasian Journal of Animal Sciences
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    • 제28권6호
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    • pp.870-875
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    • 2015
  • The purpose of this study was to investigate the alternative splicing in equine cordon-bleu WH2 repeat protein-like 1 (COBLL1) gene that was identified in horse muscle and blood leukocytes, and to predict functional consequences of alternative splicing by bioinformatics analysis. In a previous study, RNA-seq analysis predicted the presence of alternative spliced isoforms of equine COBLL1, namely COBLL1a as a long form and COBLL1b as a short form. In this study, we validated two isoforms of COBLL1 transcripts in horse tissues by the real-time polymerase chain reaction, and cloned them for Sanger sequencing. The sequencing results showed that the alternative splicing occurs at exon 9. Prediction of protein structure of these isoforms revealed three putative phosphorylation sites at the amino acid sequences encoded in exon 9, which is deleted in COBLL1b. In expression analysis, it was found that COBLL1b was expressed ubiquitously and equivalently in all the analyzed tissues, whereas COBLL1a showed strong expression in kidney, spinal cord and lung, moderate expression in heart and skeletal muscle, and low expression in thyroid and colon. In muscle, both COBLL1a and COBLL1b expression decreased after exercise. It is assumed that the regulation of COBLL1 expression may be important for regulating glucose level or switching of energy source, possibly through an insulin signaling pathway, in muscle after exercise. Further study is warranted to reveal the functional importance of COBLL1 on athletic performance in race horses.

Emerging roles of RNA and RNA-binding protein network in cancer cells

  • Kim, Mee-Young;Hur, Jung;Jeong, Sun-Joo
    • BMB Reports
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    • 제42권3호
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    • pp.125-130
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    • 2009
  • Recent advances in RNA biology reveal unexpected diversity and complexity of cellular RNA metabolism. RNA-binding proteins (RBPs) are essential players in RNA metabolism, regulating RNA splicing, transport, surveillance, decay and translation. Aberrant expression of RBPs affects many steps of RNA metabolism, significantly altering expression of RNA. Thus, altered expression and dysfuncting of RBPs are implicated in the development of various diseases including cancer. In this minireview, we briefly describe emerging roles of RBPs as a global coordinator of post-transcriptional steps and altered RBP as a global generator of cancer related RNA alternative splicing. Identification and characterization of the RNA-RBP network would expand the scope of cellular RNA metabolism and provide novel anti-cancer therapeutic targets based on cancer specific RNA-RBP interaction.

Intron retention decreases METTL3 expression by inhibiting mRNA export to the cytoplasm

  • Sangsoo Lee;Haesoo Jung;Sunkyung Choi;Namjoon Cho;Eun-Mi Kim;Kee Kwang Kim
    • BMB Reports
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    • 제56권9호
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    • pp.514-519
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    • 2023
  • Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, regulates the splicing, nuclear transport, stability, and translation of its target genes. However, the mechanism underlying the regulation of METTL3 expression by alternative splicing (AS) remains unknown. We analyzed the expression pattern of METTL3 after AS in human tissues and confirmed the expression of an isoform retaining introns 8 and 9 (METTL3-IR). We confirmed the different intracellular localizations of METTL3-IR and METTL3 proteins using immunofluorescence microscopy. Furthermore, the endogenous expression of METTL3-IR at the protein level was different from that at the mRNA level. We found that 3'-UTR generation by intron retention (IR) inhibited the export of METTL3-IR mRNA to the cytoplasm, which in turn suppressed protein expression. To the best of our knowledge, this is the first study to confirm the regulation of METTL3 gene expression by AS, providing evidence that the suppression of METTL3 protein expression by IR is an integral part of the mechanism by which 3'-UTR generation regulates protein expression via inhibition of RNA export to the cytoplasm.

RRM but not the Asp/Glu domain of hnRNP C1/C2 is required for splicing regulation of Ron exon 11 pre-mRNA

  • Moon, Heegyum;Jang, Ha Na;Liu, Yongchao;Choi, Namjeong;Oh, Jagyeong;Ha, Jiyeon;Kim, Hyeon Ho;Zheng, Xuexiu;Shen, Haihong
    • BMB Reports
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    • 제52권11호
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    • pp.641-646
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    • 2019
  • The Ron proto-oncogene is a human receptor for macrophage-stimulating protein (MSP). The exclusion of exon 11 in alternative splicing generates ${\Delta}RON$ protein that is constitutively activated. Heterogenous ribonucleaoprotein (hnRNP) $C_1/C_2$ is one of the most abundant proteins in cells. In this manuscript, we showed that both hnRNP $C_1$ and $C_2$ promoted exon 11 inclusion of Ron pre-mRNA and that hnRNP $C_1$ and hnRNP $C_2$ functioned independently but not cooperatively. Moreover, hnRNP $C_1$ stimulated exon 11 splicing through intron 10 activation but not through intron 11 splicing. Furthermore, we showed that, whereas the RRM domain was required for hnRNP $C_1$ function, the Asp/Glu domain was not. In conclusion, hnRNP $C_1/C_2$ promoted exon 11 splicing independently by stimulating intron 10 splicing through RRM but not through the Asp/Glu domain.

How are Bayesian and Non-Parametric Methods Doing a Great Job in RNA-Seq Differential Expression Analysis? : A Review

  • Oh, Sunghee
    • Communications for Statistical Applications and Methods
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    • 제22권2호
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    • pp.181-199
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    • 2015
  • In a short history, RNA-seq data have established a revolutionary tool to directly decode various scenarios occurring on whole genome-wide expression profiles in regards with differential expression at gene, transcript, isoform, and exon specific quantification, genetic and genomic mutations, and etc. RNA-seq technique has been rapidly replacing arrays with seq-based platform experimental settings by revealing a couple of advantages such as identification of alternative splicing and allelic specific expression. The remarkable characteristics of high-throughput large-scale expression profile in RNA-seq are lied on expression levels of read counts, structure of correlated samples and genes, larger number of genes compared to sample size, different sampling rates, inevitable systematic RNA-seq biases, and etc. In this study, we will comprehensively review how robust Bayesian and non-parametric methods have a better performance than classical statistical approaches by explicitly incorporating such intrinsic RNA-seq specific features with flexible and more appropriate assumptions and distributions in practice.

Splice Junction 탐색에 특화된 기존 도구들의 분석 (Analysis on Working Tools for Detecting Splice Junction)

  • 김소라;박태원;최석문;박기정;이도훈;조환규
    • 한국정보처리학회:학술대회논문집
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    • 한국정보처리학회 2011년도 추계학술발표대회
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    • pp.1119-1122
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    • 2011
  • 오늘날에는 HGP(Human Genome Project)로 인해 인간과 같은 고등생물은 높은 비율로, 단백질을 만들어낼 때 유전자 개수를 늘려 나가는 것이 아니라 유전자의 활용도를 높임으로써 다양한 단백질을 만들어낸다 새로운 사실이 밝혀졌다. 이로 인해 alternative splicing에 대한 관심이 높아지고 있다. Alternative splicing의 비중이 높아지며 이에 따라 이를 찾아내기 위한 다양한 방법들이 생겨나고, 이러한 방법 중 하나가 splice junction을 찾아내는 것이다. 본 논문에서는 splice junction 탐색을 위한 도구를 개발하기에 앞서 이미 기존에 존재하는 도구들을 조사하여 해당 도구들이 어떠한 사양과 알고리즘을 사용하는지를 분석 및 비교하였다.