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Cell Press, Molecular Cell, 6(60), p. 873-885, 2015

DOI: 10.1016/j.molcel.2015.11.011

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DGCR8 Acts as an Adaptor for the Exosome Complex to Degrade Double-Stranded Structured RNAs

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The Microprocessor complex (DGCR8/Drosha) is required for microRNA (miRNA) biogenesis but also binds and regulates the stability of several types of cellular RNAs. Of particular interest, DGCR8 controls the stability of mature small nucleolar RNA (snoRNA) transcripts independently of Drosha, suggesting the existence of alternative DGCR8 complex(es) with other nucleases to process a variety of cellular RNAs. Here, we found that DGCR8 copurifies with subunits of the nuclear exosome, preferentially associating with its hRRP6-containing nucleolar form. Importantly, we demonstrate that DGCR8 is essential for the recruitment of the exosome to snoRNAs and to human telomerase RNA. In addition, we show that the DGCR8/exosome complex controls the stability of the human telomerase RNA component (hTR/TERC). Altogether, these data suggest that DGCR8 acts as an adaptor to recruit the exosome complex to structured RNAs and induce their degradation. DGCR8 is part of the Microprocessor, a complex required for miRNA biogenesis. Macias et al. report that DGCR8 forms an alternative complex with the exosome, acting as an adaptor to recruit the exosome to mature snoRNAs and human telomerase RNA for degradation.