A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer.
The precise regulation of microRNA (miRNA) biogenesis seems to be critically important for the proper functioning of all eukaryotic organisms. Even small changes in the levels of specific miRNAs can initiate pathological processes, including carcinogenesis. Accordingly, there is a great need to deve...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3812226?pdf=render |
| _version_ | 1818247120793108480 |
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| author | Anna Kurzynska-Kokorniak Natalia Koralewska Agata Tyczewska Tomasz Twardowski Marek Figlerowicz |
| author_facet | Anna Kurzynska-Kokorniak Natalia Koralewska Agata Tyczewska Tomasz Twardowski Marek Figlerowicz |
| author_sort | Anna Kurzynska-Kokorniak |
| collection | DOAJ |
| description | The precise regulation of microRNA (miRNA) biogenesis seems to be critically important for the proper functioning of all eukaryotic organisms. Even small changes in the levels of specific miRNAs can initiate pathological processes, including carcinogenesis. Accordingly, there is a great need to develop effective methods for the regulation of miRNA biogenesis and activity. In this study, we focused on the final step of miRNA biogenesis; i.e., miRNA processing by Dicer. To test our hypothesis that RNA molecules can function not only as Dicer substrates but also as Dicer regulators, we previously identified by SELEX a pool of RNA oligomers that bind to human Dicer. We found that certain of these RNA oligomers could selectively inhibit the formation of specific miRNAs. Here, we show that these specific inhibitors can simultaneously bind both Dicer and pre-miRNAs. These bifunctional riboregulators interfere with miRNA maturation by affecting pre-miRNA structure and sequestering Dicer. Based on these observations, we designed a set of short oligomers (12 nucleotides long) that were capable of influencing pre-miRNA processing in vitro, both in reactions involving recombinant human Dicer and in cytosolic extracts. We propose that the same strategy may be used to develop effective and selective regulators to control the production of any miRNA. Overall, our findings indicate that the interactions between pre-miRNAs and other RNAs may form very complex regulatory networks that modulate miRNA biogenesis and consequently gene expression. |
| first_indexed | 2024-12-12T14:59:39Z |
| format | Article |
| id | doaj.art-7fc9fefe488045d1a1178e31570798ff |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T14:59:39Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7fc9fefe488045d1a1178e31570798ff2022-12-22T00:20:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7770310.1371/journal.pone.0077703A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer.Anna Kurzynska-KokorniakNatalia KoralewskaAgata TyczewskaTomasz TwardowskiMarek FiglerowiczThe precise regulation of microRNA (miRNA) biogenesis seems to be critically important for the proper functioning of all eukaryotic organisms. Even small changes in the levels of specific miRNAs can initiate pathological processes, including carcinogenesis. Accordingly, there is a great need to develop effective methods for the regulation of miRNA biogenesis and activity. In this study, we focused on the final step of miRNA biogenesis; i.e., miRNA processing by Dicer. To test our hypothesis that RNA molecules can function not only as Dicer substrates but also as Dicer regulators, we previously identified by SELEX a pool of RNA oligomers that bind to human Dicer. We found that certain of these RNA oligomers could selectively inhibit the formation of specific miRNAs. Here, we show that these specific inhibitors can simultaneously bind both Dicer and pre-miRNAs. These bifunctional riboregulators interfere with miRNA maturation by affecting pre-miRNA structure and sequestering Dicer. Based on these observations, we designed a set of short oligomers (12 nucleotides long) that were capable of influencing pre-miRNA processing in vitro, both in reactions involving recombinant human Dicer and in cytosolic extracts. We propose that the same strategy may be used to develop effective and selective regulators to control the production of any miRNA. Overall, our findings indicate that the interactions between pre-miRNAs and other RNAs may form very complex regulatory networks that modulate miRNA biogenesis and consequently gene expression.http://europepmc.org/articles/PMC3812226?pdf=render |
| spellingShingle | Anna Kurzynska-Kokorniak Natalia Koralewska Agata Tyczewska Tomasz Twardowski Marek Figlerowicz A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer. PLoS ONE |
| title | A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer. |
| title_full | A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer. |
| title_fullStr | A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer. |
| title_full_unstemmed | A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer. |
| title_short | A new short oligonucleotide-based strategy for the precursor-specific regulation of microRNA processing by dicer. |
| title_sort | new short oligonucleotide based strategy for the precursor specific regulation of microrna processing by dicer |
| url | http://europepmc.org/articles/PMC3812226?pdf=render |
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