A Pattern-Based Method for the Identification of MicroRNA Binding Sites and Their Corresponding Heteroduplexes

Miranda, Kevin C.; Huynh, Tien; Tay, Yvonne; Ang, Yen‐Sin; Tam, Wai Leong; Thomson, A. D.; Lim, Bing; Rigoutsos, Isidore

doi:10.1016/j.cell.2006.07.031

Cited by 1,835 publications

(1,519 citation statements)

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“…Our results address this question using a combination of experimental approaches that allowed us to monitor the cardiac levels of these splice variants in different in vivo settings. Using the rna22 algorithm (Miranda et al, 2006), we identified putative binding sites for several cardiac miRNAs (Thum et al, 2007) in the human ankrd1 intron 8 sequence suggesting that the expression of intron-8-retained and intronless ankrd1 transcripts might be differentially regulated in the heart. However, in both pig and human neonatal heart the expression of intronless and ankrd1-i8 variants was found to be similarly co-regulated in a chamber-dependent manner (see Figs.…”

Section: Discussionmentioning

confidence: 99%

Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Torrado

Iglesias

Nespereira

et al. 2009

Gene

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The cardiac ankyrin repeat domain 1 protein (ANKRD1, also known as CARP) has been extensively characterized with regard to its proposed functions as a cardio-enriched transcriptional co-factor and stressinducible myofibrillar protein. The present results show the occurrence of alternative splicing by intron retention events in the pig and human ankrd1 gene. In pig heart, ankrd1 is expressed as four alternatively spliced transcripts, three of which have non-excised introns: ankrd1-contained introns 6, 7 and 8 (i.e., ankrd1-i6,7,8), ankrd1-contained introns 7 and 8 (i.e., ankrd1-i7,8), and ankrd1 retained only intron 8 (i.e., ankrd1-i8). In the human heart, two orthologues of porcine intron-retaining ankrd1 variants (i.e., ankrd1-i8 and ankrd1-i7,8) are detected. We demonstrate that these newly-identified intron-retaining ankrd1 transcripts are functionally intact, efficiently translated into protein in vitro and exported to the cytoplasm in cardiomyocytes in vivo. In the piglet heart, both the intronless and intron-retaining ankrd1 mRNAs are co-expressed in a chamber-dependent manner being more abundant in the left as compared to the right myocardium. Our data further indicate co-upregulation of the ankrd1 spliced variants in myocardium in the porcine model of diastolic heart failure. Most significantly, we demonstrate that in vivo forced expression of recombinant intronless ankrd1 markedly increases the levels of intron-retaining ankrd1 variants (but not of the endogenous main transcript) in piglet myocardium, suggesting that ANKRD1 may positively regulate the expression of its own intron-containing RNAs in response to cardiac stress. Overall, our findings demonstrate that in cardiomyocytes ANKRD1 can exist in multiple isoforms which may contribute to the functional diversity of this factor in heart development and disease. Abbreviations ANKRD1, ankyrin repeat domain 1 protein; MARPs, muscle ankyrin repeat proteins; SRF, serum response factor; HF, heart failure; DHF, diastolic HF; LV/RV, left/right ventricular myocardium; LA/RA, left/right atrial

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Section: Discussionmentioning

confidence: 99%

Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Torrado

Iglesias

Nespereira

et al. 2009

Gene

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“…Databases for predicted target genes consisted of miRanda,26 RNA22,27 and Targetscan,28 as well as miRWalk 2.0 25. Putative target genes were identified when the miRNA‐target interactions were verified by three or more databases.…”

Section: Methodsmentioning

confidence: 99%

Maternal immune activation alters brain microRNA expression in mouse offspring

Sunwoo

Jeon²,

Moon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveMaternal immune activation (MIA) is associated with an increased risk of autism spectrum disorder (ASD) in offspring. Herein, we investigate the altered expression of microRNAs (miRNA), and that of their target genes, in the brains of MIA mouse offspring.MethodsTo generate MIA model mice, pregnant mice were injected with polyriboinosinic:polyribocytidylic acid on embryonic day 12.5. We performed miRNA microarray and mRNA sequencing in order to determine the differential expression of miRNA and mRNA between MIA mice and controls, at 3 weeks of age. We further identified predicted target genes of dysregulated miRNAs, and miRNA‐target interactions, based on the inverse correlation of their expression levels.ResultsMice prenatally subjected to MIA exhibited behavioral abnormalities typical of ASD, such as a lack of preference for social novelty and reduced prepulse inhibition. We found 29 differentially expressed miRNAs (8 upregulated and 21 downregulated) and 758 differentially expressed mRNAs (542 upregulated and 216 downregulated) in MIA offspring compared to controls. Based on expression levels of the predicted target genes, 18 downregulated miRNAs (340 target genes) and three upregulated miRNAs (60 target genes) were found to be significantly enriched among the differentially expressed genes. miRNA and target gene interactions were most significant between mmu‐miR‐466i‐3p and Hfm1 (ATP‐dependent DNA helicase homolog), and between mmu‐miR‐877‐3p and Aqp6 (aquaporin 6).InterpretationOur results provide novel information regarding miRNA expression changes and their putative targets in the early postnatal period of brain development. Further studies will be needed to evaluate potential pathogenic roles of the dysregulated miRNAs.

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“…MicroRNAs (miRNAs) are small non-coding 21-23 nucleotide RNA molecules, which regulate the production of proteins from mRNA [5,6]. They are found in the cell free fraction of blood, including serum, and can be reliably measured from frozen stored samples [7].…”

Section: Introductionmentioning

confidence: 99%

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Chiam

Wang

Watson

et al. 2015

Journal of Gastrointestinal Surgery

121

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A Pattern-Based Method for the Identification of MicroRNA Binding Sites and Their Corresponding Heteroduplexes

Cited by 1,835 publications

References 50 publications

Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Maternal immune activation alters brain microRNA expression in mouse offspring

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

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