The Microprocessor controls the activity of mammalian retrotransposons

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 - 2013/10

Y1 - 2013/10

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

SN - 1545-9993

VL - 20

SP - 1173

EP - 1181

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 10

ER -