Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs

Martin, Hilary C.; Wani, Shivangi; Steptoe, Anita L; Krishnan, K. V.; Nones, Kátia; Nourbakhsh, Ehsan; Vlassov, Alexander V.; Grimmond, Sean M.; Cloonan, Nicole

doi:10.1186/gb-2014-15-3-r51

Cited by 113 publications

(108 citation statements)

References 107 publications

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“…As shown in Table S3, the predictions indicate little overlap between the GO pathways that are enriched among the predicted targets. Although uncommon, miRNAs with the same seed can in principle have different targeting preferences that are dictated by variations outside of the seed sequence (68). For example, the members of the miR-29 family share the same seed sequence but display differences in the predicted targetomes: miR-29b localizes predominantly in the nucleus whereas miR-29a and miR-29c do not (69).…”

Section: Discussionmentioning

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.

375

365

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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: Discussionmentioning

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.

375

365

View full text Add to dashboard Cite

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“…A structurally accessible and evolutionarily conserved region (~10 nucleotides in length) was identified that alone can accurately predict AGO-mRNA associations, independent of the presence of miRNA binding sites . In any case, the impact of non-canonical targeting regarding target downregulation is not fully resolved (Khorshid et al, 2013;Martin et al, 2014;Wang, 2014). …”

Section: Non-canonical -Non-seed Interactionsmentioning

confidence: 99%

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

Pačes

Nič²,

Novotný³

et al. 2017

EFS3

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This report is the outcome of an EFSA procurement aiming at investigating and summarising the state of knowledge on (I) the mode-of-action of dsRNA and miRNA pathways, (II) the potential for nontarget gene regulation by dsRNA-derived siRNAs or miRNAs, (III) the determination of siRNA pools in plant tissues and the importance of individual siRNAs for silencing. The report is based on a comprehensive and systematic literature search, starting with the identification and retrieval of~190,000 publications related to the research area and further filtered down with keywords to produce focused collections used for subsequent screening of titles and abstracts. The report is comprised of an (I) Introduction to the field of small RNAs, (II) a Data and Methodologies section containing strategies used for literature search and study selection, and (III) the Results of the literature review organized according to the three main procurement tasks. The outcome of the first task reviews dsRNA and miRNA pathways in mammals (including humans), birds, fish, arthropods, annelids, molluscs, nematodes, and plants. Eight taxon-dedicated chapters are based on~1,400 cumulative references chosen from~10,000 inspected titles and abstracts. We review conserved and divergent aspects of small RNA pathways and dsRNA responses in animals and plants including structure and function of key proteins as well as four basic mechanisms: genome-encoded posttranscriptional regulations (miRNA), degradation of RNAs by short interfering RNA pools generated from long dsRNA (RNAi), transcriptional silencing, and sequence-independent responses to dsRNA. The outcome of the second task focuses on base pairing between small RNAs and their target RNAs and predictability of biological effects of small RNAs in animals and plants. The outcome of the last task reviews methodology, siRNA pools, and movement of small RNAs in plants. Potential transfer of small RNAs between species and circulating miRNAs in mammals is described in the final chapter.

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“…These three regions are in close proximity to each other, which was not found in the PR8 NS1 gene. It has been reported in a number of studies that miRNA can interact with the target mRNA in an imperfect seed-binding manner, albeit less frequently (Chi et al, 2012;Grimson et al, 2007;Martin et al, 2014). This might explain the inhibitory effect of the non-silencing shRNAmir on SIV/SK02 replication.…”

Section: Discussionmentioning

confidence: 93%

RNA interference of influenza A virus replication by microRNA-adapted lentiviral loop short hairpin RNA

Liu

et al. 2015

Journal of General Virology

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Limitations of the current vaccines and antivirals against influenza A virus (IAV) pandemic underscore the urgent need for developing novel anti-influenza strategies. RNA interference (RNAi) induced by small interfering RNA (siRNA) has become a powerful new means to inhibit viral infection in a gene-specific manner. However, the efficacy of the siRNA delivery platform and the relatively high cost of administration have hindered widespread application of siRNA. In this study, we developed a microRNA (miRNA)-30-based lentivirus delivery system by embedding a synthetic short hairpin RNA (shRNA) stem into the context of endogenous precursor of miRNA-30 (shRNAmir) to express a silencer of the influenza gene. We showed that the miRNA-based lentivirus vector was able to express and process a single nucleoprotein (NP)-targeting shRNAmir, which could potently inhibit IAV replication. We further showed that miRNA-based lentivirus vector carrying tandemly linked NP and polymerase PB1 shRNAmirs could express and process double shRNAmirs. Despite the relatively low levels of NP and PB1 miRNAs produced in the stably transduced cells, the combination of two miRNAs exerted a great degree of inhibition on influenza infection. Given the advantage of combinatorial RNAi in preventing emergence of mutant virus, miRNA-based lentiviral vectors are valuable tools for anitiviral activities. To the best of our knowledge, this is the first study demonstrating that a miRNA-based RNAi strategy can be applied for better control of influenza virus infection.

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Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs

Cited by 113 publications

References 107 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

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

RNA interference of influenza A virus replication by microRNA-adapted lentiviral loop short hairpin RNA

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