The Microprocessor controls the activity of mammalian retrotransposons

Sara R. Heras; Sara Macias; Mireya Plass; Noemí Fernandez; David Cano; Eduardo Eyras; José L. Garcia-Perez; Javier F. Cáceres

doi:10.1038/nsmb.2658

The Microprocessor controls the activity of mammalian retrotransposons

Sara R. Heras, Sara Macias, Mireya Plass, Noemí Fernandez, David Cano, Eduardo Eyras, José L. Garcia-Perez, Javier F. Cáceres

Computational and RNA Biology

80 Citations (Scopus)

Abstract

More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human long interspersed element 1 (LINE-1), Alu and SVA retrotransposons. Expression analyses demonstrate that cells lacking a functional Microprocessor accumulate LINE-1 mRNA and encoded proteins. Furthermore, we show that structured regions of the LINE-1 mRNA can be cleaved in vitro by Drosha. Additionally, we used a cell culture-based assay to show that the Microprocessor negatively regulates LINE-1 and Alu retrotransposition in vivo. Altogether, these data reveal a new role for the Microprocessor as a post-transcriptional repressor of mammalian retrotransposons and a defender of human genome integrity.

Original language	English
Journal	Nature Structural and Molecular Biology
Volume	20
Issue number	10
Pages (from-to)	1173-1181
Number of pages	9
ISSN	1545-9993
DOIs	https://doi.org/10.1038/nsmb.2658
Publication status	Published - Oct 2013

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title = "The Microprocessor controls the activity of mammalian retrotransposons",

abstract = "More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human long interspersed element 1 (LINE-1), Alu and SVA retrotransposons. Expression analyses demonstrate that cells lacking a functional Microprocessor accumulate LINE-1 mRNA and encoded proteins. Furthermore, we show that structured regions of the LINE-1 mRNA can be cleaved in vitro by Drosha. Additionally, we used a cell culture-based assay to show that the Microprocessor negatively regulates LINE-1 and Alu retrotransposition in vivo. Altogether, these data reveal a new role for the Microprocessor as a post-transcriptional repressor of mammalian retrotransposons and a defender of human genome integrity.",

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T1 - The Microprocessor controls the activity of mammalian retrotransposons

AU - Heras, Sara R.

AU - Macias, Sara

AU - Plass, Mireya

AU - Fernandez, Noemí

AU - Cano, David

AU - Eyras, Eduardo

AU - Garcia-Perez, José L.

AU - Cáceres, Javier F.

PY - 2013/10

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N2 - More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human long interspersed element 1 (LINE-1), Alu and SVA retrotransposons. Expression analyses demonstrate that cells lacking a functional Microprocessor accumulate LINE-1 mRNA and encoded proteins. Furthermore, we show that structured regions of the LINE-1 mRNA can be cleaved in vitro by Drosha. Additionally, we used a cell culture-based assay to show that the Microprocessor negatively regulates LINE-1 and Alu retrotransposition in vivo. Altogether, these data reveal a new role for the Microprocessor as a post-transcriptional repressor of mammalian retrotransposons and a defender of human genome integrity.

AB - More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human long interspersed element 1 (LINE-1), Alu and SVA retrotransposons. Expression analyses demonstrate that cells lacking a functional Microprocessor accumulate LINE-1 mRNA and encoded proteins. Furthermore, we show that structured regions of the LINE-1 mRNA can be cleaved in vitro by Drosha. Additionally, we used a cell culture-based assay to show that the Microprocessor negatively regulates LINE-1 and Alu retrotransposition in vivo. Altogether, these data reveal a new role for the Microprocessor as a post-transcriptional repressor of mammalian retrotransposons and a defender of human genome integrity.

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DO - 10.1038/nsmb.2658

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JO - Nature Structural and Molecular Biology

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The Microprocessor controls the activity of mammalian retrotransposons

Abstract

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