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Interplay of target site architecture and miRNA abundance determine miRNA activity and specificity

Giovanna Brancati, Sarah H. Carl, View ORCID ProfileHelge Großhans
doi: https://doi.org/10.1101/214817
Giovanna Brancati
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
2University of Basel, Basel, Switzerland.
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Sarah H. Carl
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
3Swiss Institute of Bioinformatics, Basel, Switzerland.
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Helge Großhans
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
2University of Basel, Basel, Switzerland.
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  • ORCID record for Helge Großhans
  • For correspondence: helge.grosshans@fmi.ch
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ABSTRACT

The recognition that the miRNA seed sequence is a major determinant of miRNA activity has greatly advanced the ability to predict miRNA targets. However, it has remained unclear to what extent miRNAs act redundantly when they are members of the same family and thus share a common seed. Using in vivo studies in C. elegans, we uncover features that drive specific target repression by individual miRNA family members. We find that seed-distal complementarity to a specific family member promotes specificity. However, the extent and robustness of specificity are greatly increased by seed match ‘imperfections’, such as bulges and G:U wobble base pairs. Depending on the seed match architecture, specificity may be overcome by increasing the levels of a miRNA lacking seed-distal complementarity. Hence, in contrast to a binary distinction between functional and non-functional target sites, our data support a model where functionality depends on a combination of target site quality and miRNA abundance. This emphasizes the importance of studying miRNAs under physiological conditions in their endogenous contexts.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted November 21, 2017.
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Interplay of target site architecture and miRNA abundance determine miRNA activity and specificity
Giovanna Brancati, Sarah H. Carl, Helge Großhans
bioRxiv 214817; doi: https://doi.org/10.1101/214817
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Interplay of target site architecture and miRNA abundance determine miRNA activity and specificity
Giovanna Brancati, Sarah H. Carl, Helge Großhans
bioRxiv 214817; doi: https://doi.org/10.1101/214817

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