Tumor IsomiR Encyclopedia (TIE): a pan-cancer database of miRNA isoforms

Ros, Xavier Bofill-De; Luke, Brian T.; Guthridge, Robert; Mudunuri, Uma; Loss, Michael; Gu, Shuo

doi:10.1093/bioinformatics/btab172

Cited by 15 publications

(11 citation statements)

References 53 publications

(67 reference statements)

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“…The primary analysis of miRNA expression and 5’ isomiR analysis were performed using QuagmiR on the NCI Cancer Genomics Cloud [ 43 ]. The number of 5’ isomiRs (Nseed) was calculated using an inverse Simpson diversity index [ 44 ]. This number measures the evenness of the 5’ isomiRs generated from each individual mature miRNA arm.…”

Section: Microrna Expression and 5’ Isomir Analysismentioning

confidence: 99%

Flexible pri-miRNA structures enable tunable production of 5’ isomiRs

et al. 2022

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The Drosha cleavage of a pri-miRNA defines mature microRNA sequence. Drosha cleavage at alternative positions generates 5’ isoforms (isomiRs) which have distinctive functions. To understand how pri-miRNA structures influence Drosha cleavage, we performed a systematic analysis of the maturation of endogenous pri-miRNAs and their variants both in vitro and in vivo . We show that in addition to previously known features, the overall structural flexibility of pri-miRNA impact Drosha cleavage fidelity. Internal loops and nearby G · U wobble pairs on the pri-miRNA stem induce the use of non-canonical cleavage sites by Drosha, resulting in 5’ isomiR production. By analysing patient data deposited in the Cancer Genome Atlas, we provide evidence that alternative Drosha cleavage of pri-miRNAs is a tunable process that responds to the level of pri-miRNA-associated RNA-binding proteins. Together, our findings reveal that Drosha cleavage fidelity can be modulated by altering pri-miRNA structure, a potential mechanism underlying 5’ isomiR biogenesis in tumours. Graphical Abstract

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Section: Microrna Expression and 5’ Isomir Analysismentioning

confidence: 99%

Flexible pri-miRNA structures enable tunable production of 5’ isomiRs

et al. 2022

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“…miRNASNP-v3 is another database for SNPs in miRNAs and target sites ( , accessed on 20 June 2021) [ 101 ]. Very recently, the Tumor Isomir Encyclopedia (TIE, , accessed on 20 June 2021) database was created [ 102 ], to query and compare isomiR expression across more than 11,000 tumor samples from The Cancer Genome Atlas (TCGA). Several resources for the analysis of isomiRs can be further accessed at (accessed on 20 June 2021).…”

Section: Significance Of Isomirs’ Functionsmentioning

confidence: 99%

“…Very recently, the Tumor Isomir Encyclopedia (TIE, https://isomir.ccr. cancer.gov/, accessed on 20 June 2021) database was created [102], to query and compare isomiR expression across more than 11,000 tumor samples from The Cancer Genome Atlas (TCGA). Several resources for the analysis of isomiRs can be further accessed at https://tools4mirs.org/software/isomirs_identification/ (accessed on 20 June 2021).…”

Section: Resources and Tools For Isomirs' Analysismentioning

confidence: 99%

Emerging Role of isomiRs in Cancer: State of the Art and Recent Advances

Zelli

Compagnoni

Capelli

et al. 2021

Genes

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The advent of Next Generation Sequencing technologies brought with it the discovery of several microRNA (miRNA) variants of heterogeneous lengths and/or sequences. Initially ascribed to sequencing errors/artifacts, these isoforms, named isomiRs, are now considered non-canonical variants that originate from physiological processes affecting the canonical miRNA biogenesis. To date, accurate IsomiRs abundance, biological activity, and functions are not completely understood; however, the study of isomiR biology is an area of great interest due to their high frequency in the human miRNome, their putative functions in cooperating with the canonical miRNAs, and potential for exhibiting novel functional roles. The discovery of isomiRs highlighted the complexity of the small RNA transcriptional landscape in several diseases, including cancer. In this field, the study of isomiRs could provide further insights into the miRNA biology and its implication in oncogenesis, possibly providing putative new cancer diagnostic, prognostic, and predictive biomarkers as well. In this review, a comprehensive overview of the state of research on isomiRs in different cancer types, including the most common tumors such as breast cancer, colorectal cancer, melanoma, and prostate cancer, as well as in the less frequent tumors, as for example brain tumors and hematological malignancies, will be summarized and discussed.

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“…The primary analysis of miRNA expression and 5' isomiR analysis were performed using QuagmiR on the NCI Cancer Genomics Cloud (Bofill-De Ros et al, 2019b) . The number of 5' isomiRs was calculated using an inverse Simpson diversity index (Bofill-De Ros et al, 2021) .…”

Section: Figure 5 Alternative Drosha Cleavage Is Subjected To Cellular Regulationmentioning

confidence: 99%

Flexible pri-miRNA structures enable tunable production of 5’ isomiRs

Ros

Birkenfeld

et al. 2021

Preprint

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Drosha cleavage of a pri-miRNA defines mature microRNA sequence. Drosha cleavage at alternative positions generates 5' isoforms (isomiRs) which have distinctive functions. To understand how pri-miRNA structures influence Drosha cleavage, we performed a systematic analysis of the maturation of endogenous pri-miRNAs and their variants both in vitro and in vivo. We show that, in addition to previously known features, the overall structural flexibility of pri-miRNA impacts Drosha cleavage fidelity. Internal loops and nearby G-U wobble pairs on the pri-miRNA stem induce the use of non-canonical cleavage sites by Drosha, resulting in 5' isomiR production. By analyzing patient data deposited in The Cancer Genome Atlas, we provide evidence that alternative Drosha cleavage of pri-miRNAs is a tunable process that responds to the level of pri-miRNA-associated RNA-binding proteins. Together, our findings reveal that Drosha cleavage fidelity can be modulated by altering pri-miRNA structure, a potential mechanism underlying 5' isomiR biogenesis in tumors.

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Tumor IsomiR Encyclopedia (TIE): a pan-cancer database of miRNA isoforms

Cited by 15 publications

References 53 publications

Flexible pri-miRNA structures enable tunable production of 5’ isomiRs

Flexible pri-miRNA structures enable tunable production of 5’ isomiRs

Emerging Role of isomiRs in Cancer: State of the Art and Recent Advances

Flexible pri-miRNA structures enable tunable production of 5’ isomiRs

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