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Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression

by Peter S. Linsley, Janell Schelter, Julja Burchard, Melissa M. Martin, Steven R. Bartz, Jason M, Johnson Jordan M. Cummins, Hongyue Dai, Nelson Chau, Michele Cleary, Aimee L, Michael Carleton, Lee Lim, Peter S. Linsley, Janell Schelter, Julja Burchard, Miho Kibukawa, Melissa M. Martin, Steven R. Bartz, Jason M. Johnson, Jordan M. Cummins, Christopher K. Raymond, Michael Carleton, Lee Lim , 2007
"... Supplemental material This article cites 52 articles, 20 of which can be accessed free at: ..."
Abstract - Cited by 87 (4 self) - Add to MetaCart
Supplemental material This article cites 52 articles, 20 of which can be accessed free at:
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IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions

by Anke Busch, Andreas S. Richter, Rolf Backofen - Bioinformatics , 2008
"... Motivation: During the last few years, several new small regulatory RNAs (sRNAs) have been discovered in bacteria. Most of them act as post-transcriptional regulators by base pairing to a target mRNA, causing translational repression or activation, or mRNA degradation. Numerous sRNAs have already be ..."
Abstract - Cited by 69 (15 self) - Add to MetaCart
Motivation: During the last few years, several new small regulatory RNAs (sRNAs) have been discovered in bacteria. Most of them act as post-transcriptional regulators by base pairing to a target mRNA, causing translational repression or activation, or mRNA degradation. Numerous sRNAs have already been identified, but the number of experimentally verified targets is considerably lower. Consequently, computational target prediction is in great demand. Many existing tar-get prediction programs neglect the accessibility of target sites and the existence of a seed, while other approaches are either specialized to certain types of RNAs or too slow for genome-wide searches. Results: We introduce INTARNA, a new general and fast approach to the prediction of RNA-RNA interactions incorporating accessibility of target sites as well as the existence of a user-definable seed. We suc-cessfully applied INTARNA to the prediction of bacterial sRNA targets and determined the exact locations of the interactions with a higher accuracy than competing programs.
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Thermodynamics of RNA-RNA Binding

by Ulrike Mückstein , Hakim Tafer , Jörg Hackermüller , Stephan H. Bernhart , Peter F. Stadler , Ivo L. Hofacker , 2005
"... Background: Reliable predictions of RNA-RNA binding energies is crucial e.g. for the understanding on RNAi, microRNA-mRNA binding, and antisense interactions. The thermodynamics of such RNA-RNA interactions can be understood as the sum of two energy contributions: (1) the energy necessary to “open ” ..."
Abstract - Cited by 63 (13 self) - Add to MetaCart
Background: Reliable predictions of RNA-RNA binding energies is crucial e.g. for the understanding on RNAi, microRNA-mRNA binding, and antisense interactions. The thermodynamics of such RNA-RNA interactions can be understood as the sum of two energy contributions: (1) the energy necessary to “open ” the binding site, and (2) the energy gained from hybridization. Methods: We present an extension of the standard partition function approach to RNA secondary structures that computes the probabilities Pu[i, j] that a sequence interval [i, j] is unpaired. Results: Comparison with experimental data shows that Pu[i, j] can be applied as a significant determinant of local target site accessibility for RNA interference (RNAi). Furthermore, these quantities can be used to rigorously determine binding free energies of short oligomers to large mRNA targets. The resource consumption is comparable to a single partition function computation for the large target molecule. We can show that RNAi efficiency correlates well with the binding energies of siRNAs to their respective mRNA target.

Huang W: Cellular microRNAS inhibit replication of the H1N1 influenza A virus in infected cells

by Liping Song, He Liu, Shijuan Gao, Wei Jiang, Wenlin Huang - J Virol , 2010
"... MicroRNAs (miRNAs) are a class of noncoding RNAs of lengths ranging from 18 to 23 nucleotides (nt) that play critical roles in a wide variety of biological processes. There is a growing amount of evidence that miRNAs play critical roles in intricate host-pathogen interaction networks, but the involv ..."
Abstract - Cited by 22 (0 self) - Add to MetaCart
MicroRNAs (miRNAs) are a class of noncoding RNAs of lengths ranging from 18 to 23 nucleotides (nt) that play critical roles in a wide variety of biological processes. There is a growing amount of evidence that miRNAs play critical roles in intricate host-pathogen interaction networks, but the involvement of miRNAs during influenza viral infection is unknown. To determine whether the cellular miRNAs play an important role in H1N1 influenza A viral infections, 3 � untranslated region (UTR) reporter analysis was used to identify putative miRNA targets in the influenza virus genome, and virus proliferation analysis was used to detect the effect of the screened miRNAs on the replication of H1N1 influenza A virus (A/WSN/33) in MDCK cells. The results showed that miRNA 323 (miR-323), miR-491, and miR-654 inhibit replication of the H1N1 influenza A virus through binding to the PB1 gene. Moreover mutational analysis of the predicted miRNA binding sites showed that the three miRNAs bind to the same conserved region of the PB1 gene. Intriguingly, despite the fact that the miRNAs and PB1 mRNA binding sequences are not a perfect match, the miRNAs downregulate PB1 expression through mRNA degradation instead of translation repression. This is the first demonstration that cellular miRNAs regulate influenza viral replication by degradation of the viral gene. Our findings support the notion that any miRNA has antiviral potential, independent of its cellular function, and that the cellular miRNAs play an important role in the host, defending against virus infection.
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Regulatory circuit of human microRNA biogenesis. PLoS Comput. Biol

by Ji Lee, Zhihua Li, Bino John , 2007
"... miRNAs (microRNAs) are a class of endogenous small RNAs that are thought to negatively regulate protein production. Aberrant expression of many miRNAs is linked to cancer and other diseases. Little is known about the factors that regulate the expression of miRNAs. We have identified numerous regulat ..."
Abstract - Cited by 19 (1 self) - Add to MetaCart
miRNAs (microRNAs) are a class of endogenous small RNAs that are thought to negatively regulate protein production. Aberrant expression of many miRNAs is linked to cancer and other diseases. Little is known about the factors that regulate the expression of miRNAs. We have identified numerous regulatory elements upstream of miRNA genes that are likely to be essential to the transcriptional and posttranscriptional regulation of miRNAs. Newly identified regulatory motifs occur frequently and in multiple copies upstream of miRNAs. The motifs are highly enriched in G and C nucleotides, in comparison with the nucleotide composition of miRNA upstream sequences. Although the motifs were predicted using sequences that are upstream of miRNAs, we find that 99 % of the top-predicted motifs preferentially occur within the first 500 nucleotides upstream of the transcription start sites of protein-coding genes; the observed preference in location underscores the validity and importance of the motifs identified in this study. Our study also raises the possibility that a considerable number of well-characterized, disease-associated transcription factors (TFs) of protein-coding genes contribute to the abnormal miRNA expression in diseases such as cancer. Further analysis of predicted miRNA–protein interactions lead us to hypothesize that TFs that include c-Myb, NF-Y, Sp-1, MTF-1, and AP-2a are master-regulators of miRNA expression. Our predictions are a solid starting point for the systematic elucidation of the causative basis for aberrant expression patterns of disease-related (e.g., cancer) miRNAs. Thus, we point out that focused studies of the TFs that regulate miRNAs will be paramount in developing cures for miRNA-
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Sequence analysis

by Anke Busch, Andreas S. Richter, Rolf Backofen
"... IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions ..."
Abstract - Cited by 15 (0 self) - Add to MetaCart
IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions
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Emerging Role of MicroRNAs in Cardiovascular Biology

by Michael V. G. Latronico, Daniele Catalucci, Gianluigi Condorelli, Circ Res, Michael V. G. Latronico, Daniele Catalucci, Gianluigi Condorelli
"... Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which p ..."
Abstract - Cited by 10 (0 self) - Add to MetaCart
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at:

Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma

by Nilva K. Cervigne, Patricia P. Reis, Jerry Machado, Bekim Sadikovic, Grace Bradley, Natalie Naranjo Galloni, Melania Pintilie, Igor Jurisica, Bayardo Perez-ordonez, Ralph Gilbert, Patrick Gullane, Jonathan Irish, Suzanne Kamel-reid - Hum. Mol. Genet , 2009
"... MicroRNAs (miRs) are non-coding RNA molecules involved in cancer initiation and progression. Deregulated miR expression has been implicated in cancer; however, there are no studies implicating an miR signature associated with progression in oral squamous cell carcinoma (OSCC). Although OSCC may deve ..."
Abstract - Cited by 7 (3 self) - Add to MetaCart
MicroRNAs (miRs) are non-coding RNA molecules involved in cancer initiation and progression. Deregulated miR expression has been implicated in cancer; however, there are no studies implicating an miR signature associated with progression in oral squamous cell carcinoma (OSCC). Although OSCC may develop from oral leukoplakia, clinical and histological assessments have limited prognostic value in predicting which leu-koplakic lesions will progress. Our aim was to quantify miR expression changes in leukoplakia and same-site OSCC and to identify an miR signature associated with progression. We examined miR expression changes in 43 sequential progressive samples from 12 patients and four non-progressive leukoplakias from four different patients, using TaqMan Low Density Arrays. The findings were validated using quantitative RT-PCR in an independent cohort of 52 progressive dysplasias and OSCCs, and five non-progressive dysplasias.

Exprtarget: an integrative approach to predicting human microRNA targets

by Eric R. Gamazon, Hae-kyung Im, Shiwei Duan, Yves A. Lussier, Nancy J. Cox, M. Eileen, Wei Zhang - PLoS ONE , 2010
"... Variation in gene expression has been observed in natural populations and associated with complex traits or phenotypes such as disease susceptibility and drug response. Gene expression itself is controlled by various genetic and non-genetic factors. The binding of a class of small RNA molecules, mic ..."
Abstract - Cited by 5 (1 self) - Add to MetaCart
Variation in gene expression has been observed in natural populations and associated with complex traits or phenotypes such as disease susceptibility and drug response. Gene expression itself is controlled by various genetic and non-genetic factors. The binding of a class of small RNA molecules, microRNAs (miRNAs), to mRNA transcript targets has recently been demonstrated to be an important mechanism of gene regulation. Because individual miRNAs may regulate the expression of multiple gene targets, a comprehensive and reliable catalogue of miRNA-regulated targets is critical to understanding gene regulatory networks. Though experimental approaches have been used to identify many miRNA targets, due to cost and efficiency, current miRNA target identification still relies largely on computational algorithms that aim to take advantage of different biochemical/thermodynamic properties of the sequences of miRNAs and their gene targets. A novel approach, ExprTarget, therefore, is proposed here to integrate some of the most frequently invoked methods (miRanda, PicTar, TargetScan) as well as the genome-wide HapMap miRNA and mRNA expression datasets generated in our laboratory.

The role of microRNAs in normal hematopoiesis and hematopoietic malignancies

by J Kluiver, B-j Kroesen, A Van Den Berg
"... Over the past few years, it has become evident that microRNAs (miRNAs) play an important regulatory role in various biological processes. Much effort has been put into the elucidation of their biogenesis, and this has led to the general concept that a number of key regulators are shared with the pro ..."
Abstract - Cited by 4 (0 self) - Add to MetaCart
Over the past few years, it has become evident that microRNAs (miRNAs) play an important regulatory role in various biological processes. Much effort has been put into the elucidation of their biogenesis, and this has led to the general concept that a number of key regulators are shared with the processing machinery of small interfering RNAs. Despite the recognition that several miRNAs play crucial roles in normal development and in diseases, little is known about their exact molecular function and the identity of their target genes. In this review, we report on the biological relevance of miRNAs for the differentiation of normal hematopoietic cells and on the contribution of deregulated miRNA expression in their malignant counterparts.