• Title, Summary, Keyword: mRNA

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Exploring Cancer-Specific microRNA-mRNA Interactions by Evolutionary Layered Hypernetwork Models (진화연산 기반 계층적 하이퍼네트워크 모델에 의한 암 특이적 microRNA-mRNA 상호작용 탐색)

  • Kim, Soo-Jin;Ha, Jung-Woo;Zhang, Byoung-Tak
    • Journal of KIISE:Computing Practices and Letters
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    • v.16 no.10
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    • pp.980-984
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    • 2010
  • Exploring microRNA (miRNA) and mRNA regulatory interactions may give new insights into diverse biological phenomena. Recently, miRNAs have been discovered as important regulators that play a major role in various cellular processes. Therefore, it is essential to identify functional interactions between miRNAs and mRNAs for understanding the context- dependent activities of miRNAs in complex biological systems. While elucidating complex miRNA-mRNA interactions has been studied with experimental and computational approaches, it is still difficult to infer miRNA-mRNA regulatory modules. Here we present a novel method, termed layered hypernetworks (LHNs), for identifying functional miRNA-mRNA interactions from heterogeneous expression data. In experiments, we apply the LHN model to miRNA and mRNA expression profiles on multiple cancers. The proposed method identifies cancer-specific miRNA-mRNA interactions. We show the biological significance of the discovered miRNA- mRNA interactions.

HisCoM-mimi: software for hierarchical structural component analysis for miRNA-mRNA integration model for binary phenotypes

  • Kim, Yongkang;Park, Taesung
    • Genomics & Informatics
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    • v.17 no.1
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    • pp.10.1-10.3
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    • 2019
  • To identify miRNA-mRNA interaction pairs associated with binary phenotypes, we propose a hierarchical structural component model for miRNA-mRNA integration (HisCoM-mimi). Information on known mRNA targets provided by TargetScan is used to perform HisCoM-mimi. However, multiple databases can be used to find miRNA-mRNA signatures with known biological information through different algorithms. To take these additional databases into account, we present our advanced application software for HisCoM-mimi for binary phenotypes. The proposed HisCoM-mimi supports both TargetScan and miRTarBase, which provides manually-verified information initially gathered by text-mining the literature. By integrating information from miRTarBase into HisCoM-mimi, a broad range of target information derived from the research literature can be analyzed. Another improvement of the new HisCoM-mimi approach is the inclusion of updated algorithms to provide the lasso and elastic-net penalties for users who want to fit a model with a smaller number of selected miRNAs and mRNAs. We expect that our HisCoM-mimi software will make advanced methods accessible to researchers who want to identify miRNA-mRNA interaction pairs related with binary phenotypes.

RNase P-dependent Cleavage of Polycistronic mRNAs within Their Downstream Coding Regions in Escherichia coli

  • Lee, Jung-Min;Kim, Yool;Hong, Soon-Kang;Lee, Young-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.29 no.6
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    • pp.1137-1140
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    • 2008
  • M1 RNA, the catalytic subunit of Escherichia coli RNase P, is an essential ribozyme that processes the 5' leader sequence of tRNA precursors (ptRNAs). Using KS2003, an E. coli strain generating only low levels of M1 RNA, which showed growth defects, we examined whether M1 RNA is involved in polycistronic mRNA processing or degradation. Microarray analysis of total RNA from KS2003 revealed six polycistronic operon mRNAs (acpP-fabF, cysDNC, flgAMN, lepAB, phoPQ, and puuCBE) showing large differences in expression between the adjacent genes in the same mRNA transcript compared with the KS2001 wild type strain. Model substrates spanning an adjacent pair of genes for each polycistronic mRNA were tested for RNase P cleavage in vitro. Five model RNAs (cysNC, flgMN, lepAB, phoPQ, and puuBE) were cleaved by RNase P holoenzyme but not by M1 RNA alone. However, the cleavages occurred at non-ptRNA-like cleavage sites, with much less efficiency than the cleavage of ptRNA. Since cleavage products generated by RNase P from a polycistronic mRNA can have different in vivo stabilities, our results suggest that RNase P cleavage may lead to differential expression of each cistron.

Genetic Analysis of Fission Yeast rsm1 Which is Involved in mRNA Export (분열효모에서 mRNA Export와 관련된 rgm1 유전자의 유전학적 분석)

  • Kang, Su-Ky;Yoon, Jin-Ho
    • Korean Journal of Microbiology
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    • v.44 no.2
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    • pp.98-104
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    • 2008
  • We constructed the null mutants of fission yeast Schizosaccharomyces pombe rsml gene that is thought to be involved in mRNA export. Though rsm1 gene is not essential for growth, the null mutant strain constructed by replacing the rsm1-coding region with an $kan^{r}$ gene showed growth retardation and mRNA export defects compared to wild type strain. We constructed double mutants which harbor rsm1 null allele and mutant allele of genes involved in mRNA export. The mex67 or npp106 null allele, when combined with rsm1 null allele, showed an additive effect on growth retardation and mRNA export defects. On the other hand, the thp1 null allele restored the defects of growth and mRNA export of rsm1 null mutant. These results suggest that rsm1 plays a role in mRNA export from the nucleus.

Effects of different target sites on antisense RNA-mediated regulation of gene expression

  • Park, Hongmarn;Yoon, Yeongseong;Suk, Shinae;Lee, Ji Young;Lee, Younghoon
    • BMB Reports
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    • v.47 no.11
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    • pp.619-624
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    • 2014
  • Antisense RNA is a type of noncoding RNA (ncRNA) that binds to complementary mRNA sequences and induces gene repression by inhibiting translation or degrading mRNA. Recently, several small ncRNAs (sRNAs) have been identified in Escherichia coli that act as antisense RNA mainly via base pairing with mRNA. The base pairing predominantly leads to gene repression, and in some cases, gene activation. In the current study, we examined how the location of target sites affects sRNA-mediated gene regulation. An efficient antisense RNA expression system was developed, and the effects of antisense RNAs on various target sites in a model mRNA were examined. The target sites of antisense RNAs suppressing gene expression were identified, not only in the translation initiation region (TIR) of mRNA, but also at the junction between the coding region and 3' untranslated region. Surprisingly, an antisense RNA recognizing the upstream region of TIR enhanced gene expression through increasing mRNA stability.

A new function of glucocorticoid receptor: regulation of mRNA stability

  • Park, Ok Hyun;Do, Eunjin;Kim, Yoon Ki
    • BMB Reports
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    • v.48 no.7
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    • pp.367-368
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    • 2015
  • It has long been thought that glucocorticoid receptor (GR) functions as a DNA-binding transcription factor in response to its ligand (a glucocorticoid) and thus regulates various cellular and physiological processes. It is also known that GR can bind not only to DNA but also to mRNA; this observation points to the possible role of GR in mRNA metabolism. Recent data revealed a molecular mechanism by which binding of GR to target mRNA elicits rapid mRNA degradation. GR binds to specific RNA sequences regardless of the presence of a ligand. In the presence of a ligand, however, the mRNA-associated GR can recruit PNRC2 and UPF1, both of which are specific factors involved in nonsense-mediated mRNA decay (NMD). PNRC2 then recruits the decapping complex, consequently promoting mRNA degradation. This mode of mRNA decay is termed "GR-mediated mRNA decay" (GMD). Further research demonstrated that GMD plays a critical role in chemotaxis of immune cells by targeting CCL2 mRNA. All these observations provide molecular insights into a previously unappreciated function of GR in posttranscriptional regulation of gene expression. [BMB Reports 2015; 48(7): 367-368]

Examining the Gm18 and $m^1G$ Modification Positions in tRNA Sequences

  • Subramanian, Mayavan;Srinivasan, Thangavelu;Sudarsanam, Dorairaj
    • Genomics & Informatics
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    • v.12 no.2
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    • pp.71-75
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    • 2014
  • The tRNA structure contains conserved modifications that are responsible for its stability and are involved in the initiation and accuracy of the translation process. tRNA modification enzymes are prevalent in bacteria, archaea, and eukaryotes. tRNA Gm18 methyltransferase (TrmH) and tRNA $m^1G37$ methyltransferase (TrmD) are prevalent and essential enzymes in bacterial populations. TrmH involves itself in methylation process at the 2'-OH group of ribose at the 18th position of guanosine (G) in tRNAs. TrmD methylates the G residue next to the anticodon in selected tRNA subsets. Initially, $m^1G37$ modification was reported to take place on three conserved tRNA subsets ($tRNA^{Arg}$, $tRNA^{Leu}$, $tRNA^{Pro}$); later on, few archaea and eukaryotes organisms revealed that other tRNAs also have the $m^1G37$ modification. The present study reveals Gm18, $m^1G37$ modification, and positions of $m^1G$ that take place next to the anticodon in tRNA sequences. We selected extremophile organisms and attempted to retrieve the $m^1G$ and Gm18 modification bases in tRNA sequences. Results showed that the Gm18 modification G residue occurs in all tRNA subsets except three tRNAs ($tRNA^{Met}$, $tRNA^{Pro}$, $tRNA^{Val}$). Whereas the $m^1G37$ modification base G is formed only on $tRNA^{Arg}$, $tRNA^{Leu}$, $tRNA^{Pro}$, and $tRNA^{His}$, the rest of the tRNAs contain adenine (A) next to the anticodon. Thus, we hypothesize that Gm18 modification and $m^1G$ modification occur irrespective of a G residue in tRNAs.

Effects of spTho1 Deletion and Over-Expression on mRNA Export in Fission Yeast (분열효모에서 spTho1 유전자의 결실과 과발현이 생장 및 mRNA Export에 미치는 영향)

  • Cho, Ye-Seul;Yoon, Jin-Ho
    • Korean Journal of Microbiology
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    • v.46 no.4
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    • pp.401-404
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    • 2010
  • Tho1 is a RNA-binding protein that assembles co-transcriptionally onto the nascent mRNA and is thought to be involved in mRNP biogenesis and mature mRNA export to cytoplasm in budding yeast. In fission yeast Schizosaccharomyces pombe, a homologue of THO1 (spTho1) was identified based on sequence alignment. A deletion mutant in a diploid strain was constructed by replacing one of spTho1-coding region with an ura4+ gene using one-step gene disruption method. Tetrad analysis showed that the spTho1 was not essential for growth. The spTho1 mutant did not show any defects of bulk mRNA export. However, over-expression of spTho1 from strong nmt1 promoter caused the growth defects and accumulation of poly(A)$^+$ RNA in the nucleus. These results suggest that spTho1 is involved in mRNA export from the nucleus to cytoplasm though it is not essential.

Selection of Yeast Mutant Strain with High RNA Content and Its High Cell-Density Fed-Batch Culture. (고함량 RNA 효모 변이주의 선별 및 고농도세포 유가배양)

  • 김재범;권미정;남희섭;김재훈;남수완
    • Microbiology and Biotechnology Letters
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    • v.30 no.1
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    • pp.68-72
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    • 2002
  • To obtain a yeast mutant with high RNA content and high growth rate, Saccharomyces cerevisiae MTY62 was mutated with ethylmethane sulfonate. Among the selected mutants that were sensitive to the high concentration of KCl, M40-10 strain was finally selected due to its rapid cell growth and high RNA content in the tube and baffled-flask cultures. In the batch culture of M40-10 mutant, the maximum specific growth rate ($\mu_{max}$) of $0.38 h^{-1}$ , RNA concentration of 3210 mg-RNA/1, and RNA content of 183 mg-RNA/g-DCW were obtained, which were 23%, 15%, and 12% increased levels, respectively, compared to those of MTY62 parent strain. The intermittent fed-batch culture of M40-10 strain resulted in the maximum cell concentration of 35.6 g-DCW/1, RNA concentration of 5677 mg/1, and RNA content of 160 mg-RNA/g-DCW. Through the constant fed-batch culture, the maximum cell concentration of 46.4 g-DCW/1, RNA concentration of 6270 mg-RNA/1, and RNA content of 135 mg-RNA/g-DCW were obtained. At the 20 h culture time in the fed-batch cultures of M40-10 strain, the cell and RNA concentrations were increased by 30% and 10%, respectively, over the parent strain MTY62. In addition, it was also found that the accumulated RNA within the mutant cell was not degraded until the end of fed-batch cultivation, indicating that the M40-10 cell is a mutant with weak acidic RNase activity.y.

Biosynthesis of messenger RNA in aspergillus phoenicis during thier life cycle (Aspergillus phoenicis의 생활사를 통한 mRNA의 생합성)

  • 김봉수;이영록
    • Korean Journal of Microbiology
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    • v.26 no.1
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    • pp.27-31
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    • 1988
  • Biosynthesis and processing of cytoplasmic mRNA from heterogenous nuclear RNA (hn-RNA) in Aspergillus phoenicis were studied by $^{3}H$-uridine labeling and synchronous culture techniques during their life cycle. Incorporations of $^{3}H$-uridine into hn-RNA and mRNA were most rapid in vesicle-phialide fromation stage and diminished in hyphal growth stage. The processing of cytoplasmic mRNA from hn-RNA was proceeded more rapidly in hyphal growth and conidiophore formation stages than in conidia and vesicle-phialide formation stages. The specific radioactivities of hn-RNA and mRNA were very high in vesicle-phialide formation stage.

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