The Microprocessor controls the activity of mammalian retrotransposons
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The Microprocessor controls the activity of mammalian retrotransposons. / Heras, Sara R.; Macias, Sara; Plass, Mireya; Fernandez, Noemí; Cano, David; Eyras, Eduardo; Garcia-Perez, José L.; Cáceres, Javier F.
I: Nature Structural and Molecular Biology, Bind 20, Nr. 10, 2013, s. 1173-1181.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
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
Y1 - 2013
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.
U2 - 10.1038/nsmb.2658
DO - 10.1038/nsmb.2658
M3 - Journal article
C2 - 23995758
VL - 20
SP - 1173
EP - 1181
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 10
ER -
ID: 50802314