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Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops
We recently found that hnRNP A1, a protein implicated in many aspects of RNA processing, acts as an auxiliary factor for the Drosha-mediated processing of a microRNA precursor, pri-miR-18a. Here, we provide the mechanism by which hnRNP A1 regulates this event. We show that hnRNP A1 binds to the loop...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631628/ https://www.ncbi.nlm.nih.gov/pubmed/18995836 http://dx.doi.org/10.1016/j.molcel.2008.10.013 |
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author | Michlewski, Gracjan Guil, Sonia Semple, Colin A. Cáceres, Javier F. |
author_facet | Michlewski, Gracjan Guil, Sonia Semple, Colin A. Cáceres, Javier F. |
author_sort | Michlewski, Gracjan |
collection | PubMed |
description | We recently found that hnRNP A1, a protein implicated in many aspects of RNA processing, acts as an auxiliary factor for the Drosha-mediated processing of a microRNA precursor, pri-miR-18a. Here, we provide the mechanism by which hnRNP A1 regulates this event. We show that hnRNP A1 binds to the loop of pri-miR-18a and induces a relaxation at the stem, creating a more favorable cleavage site for Drosha. We found that approximately 14% of all pri-miRNAs have highly conserved loops, which we predict act as landing pads for trans-acting factors influencing miRNA processing. In agreement, we show that 2′O-methyl oligonucleotides targeting conserved loops (LooptomiRs) abolish miRNA processing in vitro. Furthermore, we present evidence to support an essential role of conserved loops for pri-miRNA processing. Altogether, these data suggest the existence of auxiliary factors for the processing of specific miRNAs, revealing an additional level of complexity for the regulation of miRNA biogenesis. |
format | Text |
id | pubmed-2631628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26316282009-01-30 Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops Michlewski, Gracjan Guil, Sonia Semple, Colin A. Cáceres, Javier F. Mol Cell Article We recently found that hnRNP A1, a protein implicated in many aspects of RNA processing, acts as an auxiliary factor for the Drosha-mediated processing of a microRNA precursor, pri-miR-18a. Here, we provide the mechanism by which hnRNP A1 regulates this event. We show that hnRNP A1 binds to the loop of pri-miR-18a and induces a relaxation at the stem, creating a more favorable cleavage site for Drosha. We found that approximately 14% of all pri-miRNAs have highly conserved loops, which we predict act as landing pads for trans-acting factors influencing miRNA processing. In agreement, we show that 2′O-methyl oligonucleotides targeting conserved loops (LooptomiRs) abolish miRNA processing in vitro. Furthermore, we present evidence to support an essential role of conserved loops for pri-miRNA processing. Altogether, these data suggest the existence of auxiliary factors for the processing of specific miRNAs, revealing an additional level of complexity for the regulation of miRNA biogenesis. Cell Press 2008-11-07 /pmc/articles/PMC2631628/ /pubmed/18995836 http://dx.doi.org/10.1016/j.molcel.2008.10.013 Text en © 2008 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Michlewski, Gracjan Guil, Sonia Semple, Colin A. Cáceres, Javier F. Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops |
title | Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops |
title_full | Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops |
title_fullStr | Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops |
title_full_unstemmed | Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops |
title_short | Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops |
title_sort | posttranscriptional regulation of mirnas harboring conserved terminal loops |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631628/ https://www.ncbi.nlm.nih.gov/pubmed/18995836 http://dx.doi.org/10.1016/j.molcel.2008.10.013 |
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