A uniform system for microRNA annotation

Ambros, Victor R.; Bartel, Bonnie; Bartel, David P.; Burge, Christopher B.; Carrington, James C.; Chen, Xuemei; Dreyfuss, Gideon; Eddy, Sean R.; Griffiths-Jones, Sam; Marshall, Mhairi; Matzke, Marjori; Ruvkun, Gary; Tuschl, Thomas

doi:10.1261/rna.2183803

Cited by 1,647 publications

(1,092 citation statements)

References 18 publications

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“…The total number of miR-I clones from the sequenced plasmids almost equaled that of total endogenous cellular miRNAs (Table S1), indicating that miR-I was highly expressed and efficiently processed by Drosha and Dicer. miR-I meets all of the criteria used to identify miRNAs (16). Thus, it is clear that the HSV-2 primary LAT is a primary miRNA gene, which may explain why spliced LAT is very difficult to detect as compared to the LAT intron, even though the LAT promoter is highly active during latency.…”

Section: Discussionmentioning

confidence: 99%

An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor

Tang

Bertke

Patel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

164

213

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Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression.HSV ͉ latency-associated transcript ͉ latency ͉ reactivation ͉ human H erpes simplex virus 1 and 2 (HSV-1 and HSV-2) are closely related human herpes viruses. HSV-1 and HSV-2 establish lifelong incurable latency in and reactivate preferentially from trigeminal ganglia and dorsal root ganglia to cause oro-facial and genital herpes, respectively. Although infections are usually mild, these viruses can cause severe disease including encephalitis and neonatal herpes, and HSV-2 infection is a risk factor for HIV acquisition. The only readily detectable viral transcript during latency of both HSV-1 and HSV-2 is the noncoding latency-associated transcript (LAT), which is transcribed from within the long repeats of the viral genome ( Fig. 1) (1). A Ϸ8-kb primary LAT is spliced, yielding a stable Ϸ2-kb LAT intron (2). Deletion of the LAT promoter in both HSV-1 and HSV-2 reduces the efficiency of reactivation (3-5), and substitution of HSV-1 LAT for native HSV-2 LAT sequences confers an HSV-1 reactivation phenotype (6). The HSV-1 LAT is currently believed to act in part by increasing the establishment or maintenance of latency, likely via an effect on the survival of acutely infected neurons (7), which may be mediated by inhibition of apoptosis in infected neurons (8). The molecular function of HSV-2 LAT remains largely unknown.miRNAs are a family of 21Ϸ24-nt noncoding RNAs that regulate gene expression based on sequence similarity to their targets. Mammalian viruses including EBV, Kaposi's sarcoma-associated herpesvirus, human cytomegalovirus, and SV40 encode viral miRNAs (9). Viral encoded miRNAs were predicted for HSV-1 (10, 11) and also for HSV-2 (10). However, no miRNAs have been identified in HSV-2 or HSV-1 LAT sequences. Results HSV-2 LAT Exon 2 Encodes a miRNA.To find miRNAs within the HSV-2 LAT region, a plasmid containing the LAT sequence and its promoter (pSSK) and a mutant plasmid expressing LAT under control of the CMV-IE promoter (pCMV-SSK) were transfected into 293 cells. Small RNAs isolated from the transfected cells were cloned and sequenced. A 22-23-nt HSV-2 RNA sequence (designated HSV-2 miR-I) appeared at a frequenc...

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Section: Discussionmentioning

confidence: 99%

An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor

Tang

Bertke

Patel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

164

213

View full text Add to dashboard Cite

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“…MicroRNAs (miRNA) are 18-24 nucleotides single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to the target messenger RNAs to regulate gene expression [14][15][16]. There is growing evidence that miRNAs regulate hematopoiesis in both hematopoietic stem cells and committed progenitor cells [17][18][19][20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

Zhan

Cardozo

et al. 2013

Blood Cells, Molecules, and Diseases

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Polycythemia vera (PV) and essential thrombocythemia (ET) are the two most common myeloproliferative neoplasms. The same JAK2 V617F mutation can be found in both disorders and is able to recapitulate many of the phenotypic abnormalities of these diseases in the murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18-24 nucleotides single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. We performed miRNA expression profiling by oligonucleotide microarray analysis in purified peripheral blood CD34+ cells from eight JAK2 V617F -positive PV patients and six healthy donors. A quantitative reverse-transcription polymerase chain reaction assay was used to verify differential miRNA expression. Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the early erythroid progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in PV CD34+ cells and confirm a genetic basis for the gender-specific differences that characterize PV with respect to miRNA. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined.

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“…Analogous to miRNAs, siRNAs are bound to Argonaute proteins Martinez et al 2002) and may also assemble with additional proteins to form RNAinduced silencing complexes (RISCs; Hammond et al 2001). siRNAs and miRNAs (and RISCs and miRNPs) are functionally equivalent, and the main difference between the two classes of small RNAs are the fact that miRNAs are derived from endogenous genes (Ambros et al 2003a).…”

mentioning

confidence: 99%

A combined computational-experimental approach predicts human microRNA targets

Kiriakidou¹,

Nelson²,

Kouranov³

et al. 2004

Genes Dev.

709

502

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A new paradigm of gene expression regulation has emerged recently with the discovery of microRNAs (miRNAs). Most, if not all, miRNAs are thought to control gene expression, mostly by base pairing with miRNA-recognition elements (MREs) found in their messenger RNA (mRNA) targets. Although a large number of human miRNAs have been reported, many of their mRNA targets remain unknown. Here we used a combined bioinformatics and experimental approach to identify important rules governing miRNA-MRE recognition that allow prediction of human miRNA targets. We describe a computational program, "DIANA-microT", that identifies mRNA targets for animal miRNAs and predicts mRNA targets, bearing single MREs, for human and mouse miRNAs. bros 1999;Seggerson et al. 2002;Zeng et al. 2002;Doench et al. 2003). The manner by which a miRNA or siRNA base pairs with its mRNA target correlates with its function: if the complementarity between a miRNA and its target is extensive, the RNA target is cleaved (Hutvagner and Zamore 2002;Llave et al. 2002;Rhoades et al. 2002;Tang et al. 2003;Xie et al. 2003); if the complementarity is partial, the stability of the target mRNA in not affected but its translation is repressed (Olsen and Ambros 1999;Seggerson et al. 2002;Zeng et al. 2002;Doench et al. 2003). However, how general this correlation is and the factors and mechanisms that determine the function of any given miRNA are unknown.

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A uniform system for microRNA annotation

Cited by 1,647 publications

References 18 publications

An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor

An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

A combined computational-experimental approach predicts human microRNA targets

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