Modulation of microrna processing by mismatch repair protein mutl. Role of micrornas in tumorigenesis and their modulation by versican 3 untranslated region daniel yenhong lee doctor of philosophy laboratory medicine and pathobiology university of toronto 2010 abstract microrna is a singlestranded rna of about 22 nucleotides in length and is expressed endogenously. Microrna controls expression of oncogenes a new study demonstrates that micrornas can modulate the expression of well known tumorspecific. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Determinants of microrna processing inhibition by the. Mar 12, 2015 nutlin3 induces p53 regulated mirnas and p53 responsive genes. Micrornas and essential components of the microrna processing. Some men have this defect all over their bodies, but in women it is usually expressed in a peculiar way. The transcription regulation of specific mirnas by p53. Modulation of microrna expression and function by adars.
Regulation of microrna expression and function by nuclear. The processing of plant precursors by multiple dcl1 cuts has been also observed in other cases 28, 82 and so far, is a distinctive feature not present in animal precursors. The binding of microrna mirna, or mir to the 3untranslated region of target mrnas causes transcript degradation or interferes with translation initiation. Repression of transposableelements a microrna anticancer. This plugin allows you to do on the fly extension of a pathway with regulatory information.
Methods for further details and supplementary data file 1 for the mirna. These findings suggest that transcriptionindependent modulation of mirna. Functional and pathway enrichment analyses were performed using the david program. The differentially expressed mirna and genes were accessed by a geo2r. Pathvisio allows you to do pathway analysis on pathways from wikipathways and others once you get them in the right format. Disruption of p53 function is a fundamental event in the development of. They are first transcribed as much longer primary transcripts, which then undergo a series of processing steps to yield the singlestranded, mature micrornas, although the mechanisms are incompletely understood. Modulation of microrna processing by p53 toru suzuki, hiroshi tamada department of cancer biology, graduate school of medicine, kyoto university, kyoto, japan this article has been withdrawn at the request of the editor. The p53 protein is known to activate the transcription of a subset of mirna. Interplay between reactive oxygen species and micrornas in. Experiments with different cell types show that the p53 pathway regulates cell fate through a switch behavior in its dynamics. P53 was found to be able to modulate microrna maturation by associating with drosha, enhancing the binding and processing capability of the drosha complex on some primirnas 64,65. The role of mir2 in microrna processing german leonova, richard greavesa, jon timmisb, dimitris lagosa university of york.
Utr, a major docking platform for mirnas, is regulated by alternative polyadenylation. Drosha plays a key role in the generation of precursor micrornas from primary microrna primirna transcripts in animal cells, yet how drosha recognizes its rna substrates remains incompletely understood. First, we examined the processing of two primirna substrates that were labeled at their 5 or 3 termini fig. Besides the transcriptional regulation p53 plays on micrornas, it is also involved in the biogenesis and function of some micrornas. Lin28 inhibits the maturation of the let7 family but not other mirnas, yet a mechanistic explanation for this selectivity is unknown. Please use one of the following formats to cite this article in your essay, paper or report. Dna damage induces cell cycle checkpoints that activate the p53 pathway to regulate cell fate mechanisms such as apoptosis or senescence. This posttranscriptional inhibitory mechanism is of critical importance in fundamental cell processes, including development, proliferation, survival and death. The p53 protein is known to activate the transcription of a subset of mirnacoding genes 1,3,5. Jun 09, 2008 microrna controls expression of oncogenes a new study demonstrates that micrornas can modulate the expression of well known tumorspecific oncogenic translocation proteins and may play a.
All relevant data are within the paper and its supporting information files. The production of mrna isoforms with a different 3. However, the role of mirna in osteoblast mechanotransduction remains to be. Dna damage induces cell cycle checkpoints that activate the p53. Growing evidence suggests that mirnas can be regulated extensively at the levels of promoter transcription, methylation, mirna processing, rna editing, and mirna target interactions. Genome wide expression profiling of p53 regulated mirnas in. Integration of micrornamrna profiles and pathway analysis of plant isoquinoline alkaloid berberine in sgc7901 gastric cancers cells yanhong yang,1 na zhang,2 kundong li,2 juan chen,2 lang qiu,1 jufeng zhang2 1the first affiliated hospital, school of clinical medicine, guangdong pharmaceutical university, guangzhou, peoples republic of china.
Jul 23, 2009 the p53 tumour suppressor is a well known transcriptional activator with many growth suppressive targets. Among these we found well studied molecules, such as the mir1792 cluster, comprising potent oncogenic microrna, and mir34, recently found to interact with p53. Researchers at tufts university school of medicine and tufts medical center have identified an rna sequence that. To identify key micrornas mirnas and their regulatory networks in prostate cancer. The maturation of mirnas is a complex process, which includes the. Taqman microrna profiling using 384well array cards thermo.
Modulation of microrna processing by p53 article pdf available in nature 4607254. Overview of microrna processing, from transcription to the formation of the effector complex. The p53 tumour suppressor is a well known transcriptional activator with many growth suppressive targets. Transcriptional regulation by nuclear receptors is the primary level of control for mirna expression table 1. In particular we describe how a new transcriptionally independent function of mutant p53 in mirna maturation, through a mechanism by which this oncogene is able to interfere with the drosha processing machinery, generally inhibits mirna processing in cancer and consequently impacts on carcinogenesis.
Altered mirna levels may be caused by regulatory proteins that influence mirna processing, acquired variations in the mirna transcript, and by changes in the nuclear export efficiency. Suzuki hi, yamagata k, sugimoto k, iwamoto t, kato s, miyazono k. Micrornas and essential components of the microrna processing machinery are not encoded in the genome of the ctenophore mnemiopsis leidyi maxwell et al. Highthroughput assessment of microrna activity and function. Disruption of p53 function is a fundamental event in the development of most cancers. The developmentally regulated rnabinding protein lin28 was recently identified as a selective inhibitor of mirna processing in embryonic stem cells and embryonal carcinoma cells. In principle, the processing of mir319 and mir159 precursors might lead to the accumulation of several mirnas. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between drosha complex and p68, leading to attenuation of mirna processing activity. Aug 23, 2018 please use one of the following formats to cite this article in your essay, paper or report. Researchers at tufts university school of medicine and tufts medical center have identified an. Recent studies have demonstrated that mirnas interact with p53 and its network. The publisher apologizes for any inconvenience this may cause. Altered microrna expression was detected for a total of 72 micrornas. Whether that is useful to you depends on what you want to do.
Identification of the key micrornas and the mirnamrna. Key modulators of posttranscriptional gene expression steven p. These findings suggest that transcriptionindependent modulation of mirna biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Dec 19, 2012 furthermore, the current status of the research on the connection between p53 and mirnas, as well as alterations in the p53 mirna pathways found in cancer will be summarized and discussed. Primary microrna processing is functionally coupled to rnap. Genome wide expression profiling of p53 regulated mirnas. Navigating the micronome using multiple microrna prediction. Jul 15, 2011 yang w, chendrimada tp, wang q, higuchi m, seeburg ph, shiekhattar r, nishikura k 2006 modulation of microrna processing and expression through rna editing by adar deaminases. Highthroughput assessment of microrna activity and function using microrna sensor and decoy libraries gavriel mullokandov, alessia baccarini, albert ruzo, anitha d jayaprakash, navpreet tung, benjamin israelow, matthew j evans, ravi sachidanandam, brian d brown supplementary file title supplementary figure 1 bdlvbased mirna sensor library.
Four mirna and three gene expression microarray datasets were downloaded for analysis from gene expression omnibus database. Here, we show that the terminal loop region of human primary microrna transcripts is an important determinant of microrna biogenesis. B regulate microrna34c expression in porcine ovarian granulosa cells. Cell fate regulation is an open problem whose comprehension impacts several areas of the biosciences.
Navigating the micronome using multiple microrna prediction databases to identify signalling pathwayassociated micrornas elize a. Integration of micrornamrna profiles and pathway analysis of. Microrna16 feedback loop with p53 and wip1 can regulate cell. Processing of plant microrna precursors briefings in. This study raises a possibility that p53 functions as a global modifier of gene expression through the regulation of mirna processing. Microrna control of p53 juan liu, cen zhang, yuhan zhao, and zhaohui feng department of radiation oncology, rutgers cancer institute of new jersey, rutgers, state university of new jersey, new brunswick 08903, new jersey abstract tumor suppressor p53 plays a central role in tumor suppression. In addition, human lung adenocarcinomas generate an elevated level of a short hdm4 isoform through alternative polyadenylation. Efficient processing of primary microrna hairpins by drosha. Cleavage of pribantam or primir30a yielded the expected end. Processing of mirnas can be regulated at multiple steps and leads to either elevated or decreased mirna levels. Modulation of microrna processing by p53 hiroshi i. Newly identified rna sequence is key in microrna processing.
Jul 23, 2009 we also found that transcriptionally inactive p53 mutants interfere with a functional assembly between drosha complex and p68, leading to attenuation of mirna processing activity. Emerging evidence indicates that micrornas mirnas play essential roles in regulating osteoblastogenesis and bone formation. The importance of the p53 mir34hdm4 feedback loop is further confirmed by an inverse correlation between mir34 and fulllength hdm4 in human lung adenocarcinomas. Taqman array microrna cards using classic chemistry include coverage of the most relevant microrna for human or rodent species, aligned with sanger mirbase v22, with over 740 assays enabled across the sets of taqman array microrna cards cards a and b. Pdf micrornas mirnas have emerged as key posttranscriptional regulators of gene expression, involved in diverse physiological and. Some men have this defect all over their bodies, but in. Xu yuan 1, zhang ailing 2, xiao guang 1, zhang zhe 1, chen zanmou 1, zhang hao 1, li jiaqi 1. Drosha is a member of the ribonuclease rnase iii family that selectively processes rnas with prominent doublestranded features. Modulation of microrna processing by p53 researchgate. Bibliographical references of molecular interactions in the model. Pdf modulation of microrna processing by p53 researchgate. The tumor suppressor protein p53 was recently identified to modulate mirna processing through association with p68 and drosha, similar to. Aug 16, 2010 newly identified rna sequence is key in microrna processing.
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