Specific sequence determinants of miR-15/107 microRNA gene group targets

Nelson, Peter T.; Wang, Wang‐Xia; Mao, Guogen; Wilfred, Bernard R.; Xie, Kevin; Jennings, Mary H.; Z, Gao; Wang, Xiaowei

doi:10.1093/nar/gkr532

Cited by 48 publications

(40 citation statements)

References 38 publications

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“…These targets include loci in the protein-coding region of mRNAs (8)(9)(10)(11)(12)(13), 5′ UTRs (14), intronic and intergenic transcripts (15,16), and other non-protein-coding RNAs (ncRNAs) (17,18), as well as embedded B retroelements (13,19), pseudogenes (20), short interspersed elements (SINEs) (21), and circular RNAs (22,23). As technological and research advances reveal a larger and more diverse spectrum of miRNA targets, the related question of how many miRNAs are encoded by an organism's genome becomes one of renewed importance.…”

Section: Significancementioning

confidence: 99%

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs

Londin

Lohera

Telonis

et al. 2015

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

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377

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Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples. Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons. Of these novel miRNAs, 1,657 (45%) were identified in 43 datasets that were generated by cross-linking followed by Argonaute immunoprecipitation and sequencing (Ago CLIP-seq) and represented 3 of the 13 tissues, indicating that these miRNAs are active in the RNA interference pathway. Moreover, experimental investigation through stemloop PCR of a random collection of newly discovered miRNAs in 12 cell lines representing 5 tissues confirmed their presence and tissue dependence. Among the newly identified miRNAs are many novel miRNA clusters, new members of known miRNA clusters, previously unreported products from uncharacterized arms of miRNA precursors, and previously unrecognized paralogues of functionally important miRNA families (e.g., miR-15/107). Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7% of the newly discovered miRNAs to be human-specific whereas the majority (94.4%) are primate lineage-specific. Our findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage-and/or tissue-specific miRNAs that are uncharacterized. SignificanceMicroRNAs (miRNAs) are small ∼22-nt RNAs that are important regulators of posttranscriptional gene expression. Since their initial discovery, they have been shown to be involved in many cellular processes, and their misexpression is associated with disease etiology. Currently, nearly 2,800 human miRNAs are annotated in public repositories. A key question in miRNA research is how many miRNAs are harbored by the human genome. To answer this question, we examined 1,323 short RNA sequence samples and identified 3,707 novel miRNAs, many of which are human-specific and tissue-specific. Our findings suggest that the human genome expresses a greater number of miRNAs than has previously been appreciated and that many more miRNA molecules may play key roles in disease etiology.

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Section: Significancementioning

confidence: 99%

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs

Londin

Lohera

Telonis

et al. 2015

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

Self Cite

377

365

View full text Add to dashboard Cite

show abstract

“…“RIP-ChIP” (AGO protein immunoprecipitation, which pulls down miRNAs and mRNA targets, followed by high density microarray) revealed that members of the miR-103/107 family preferentially bind their target CDS [19]. Individual miRNAs also recognize CDS targets.…”

Section: Mirna Biogenesis and Regulationmentioning

confidence: 99%

miRNAs and estrogen action

Klinge

2012

Trends in Endocrinology & Metabolism

181

130

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MicroRNAs (miRNAs) are short, non-coding RNAs that generally base-pair within the 3′ untranslated region of target mRNAs causing translational inhibition and/or mRNA degradation. Estradiol (E2) and other estrogen receptor (ER) ligands suppress or stimulate miRNA expression in human breast cancer cells, endometrial cells, rat mammary gland, and mouse uterus and post-translationally regulate protein expression. Aberrant miRNA expression is implicated in estrogen-related breast and endometrial cancers and a number of miRNAs downregulate ERα. The role of estrogen-regulated miRNA expression, the target genes of these miRNAs, and the role of miRNAs in health and disease is a “hot” area of research that will yield new insight into molecular mechanisms of estrogen action.

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“…Until recently, active animal miRNA recognition sites were thought to be present solely within the 3’ UTR of an mRNA. However, recent evidence has suggested that sites also exist in the 5’ UTR [15], within the coding sequence [16], and in some cases these sites may be present in multiple locations within a transcript. Target prediction algorithms are undoubtedly valuable tools to researchers in the field providing a rapid appreciation of the potential processes impacted by a particular miRNA and prioritising potential direct targets for validation assays.…”

Section: Introductionmentioning

confidence: 99%

Integrated miRNA, mRNA and protein expression analysis reveals the role of post-transcriptional regulation in controlling CHO cell growth rate

et al. 2012

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BackgroundTo study the role of microRNA (miRNA) in the regulation of Chinese hamster ovary (CHO) cell growth, qPCR, microarray and quantitative LC-MS/MS analysis were utilised for simultaneous expression profiling of miRNA, mRNA and protein. The sample set under investigation consisted of clones with variable cellular growth rates derived from the same population. In addition to providing a systems level perspective on cell growth, the integration of multiple profiling datasets can facilitate the identification of non-seed miRNA targets, complement computational prediction tools and reduce false positive and false negative rates.Results51 miRNAs were associated with increased growth rate (35 miRNAs upregulated and 16 miRNAs downregulated). Gene ontology (GO) analysis of genes (n=432) and proteins (n=285) found to be differentially expressed (DE) identified biological processes driving proliferation including mRNA processing and translation. To investigate the influence of miRNA on these processes we combined the proteomic and transcriptomic data into two groups. The first set contained candidates where evidence of translational repression was observed (n=158). The second group was a mixture of proteins and mRNAs where evidence of translational repression was less clear (n=515). The TargetScan algorithm was utilised to predict potential targets within these two groups for anti-correlated DE miRNAs.ConclusionsThe evidence presented in this study indicates that biological processes such as mRNA processing and protein synthesis are correlated with growth rate in CHO cells. Through the integration of expression data from multiple levels of the biological system a number of proteins central to these processes including several hnRNPs and components of the ribosome were found to be post-transcriptionally regulated. We utilised the expression data in conjunction with in-silico tools to identify potential miRNA-mediated regulation of mRNA/proteins involved in CHO cell growth rate. These data have allowed us to prioritise candidates for cell engineering and/or biomarkers relevant to industrial cell culture. We also expect the knowledge gained from this study to be applicable to other fields investigating the role of miRNAs in mammalian cell growth.

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Specific sequence determinants of miR-15/107 microRNA gene group targets

Cited by 48 publications

References 38 publications

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs

miRNAs and estrogen action

Integrated miRNA, mRNA and protein expression analysis reveals the role of post-transcriptional regulation in controlling CHO cell growth rate

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