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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.

SUBMITTER: Heras SR 

PROVIDER: S-EPMC3836241 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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The Microprocessor controls the activity of mammalian retrotransposons.

Heras Sara R SR   Macias Sara S   Plass Mireya M   Fernandez Noemí N   Cano David D   Eyras Eduardo E   Garcia-Perez José L JL   Cáceres Javier F JF  

Nature structural & molecular biology 20130901 10


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  ...[more]

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