Mpp6 Incorporation in the Nuclear Exosome Contributes to RNA Channeling through the Mtr4 Helicase
| Autor: | Fabien Bonneau, Sebastian Falk, Alexander Kögel, Judith Ebert, Elena Conti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RNase P Exosome complex Ribosome biogenesis ribosome biogenesis RNA-binding protein Crystallography X-Ray Exosomes General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Report Humans exosome lcsh:QH301-705.5 X-ray crystallography Cell Nucleus Genetics biology pontocerebellar hypoplasia 1. No poverty Membrane Proteins Helicase RNA KH domain Cell biology helicase 030104 developmental biology lcsh:Biology (General) TRAMP complex biology.protein Ribosomes RNA Helicases 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 20, Iss 10, Pp 2279-2286 (2017) Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Summary The RNA-degrading exosome mediates the processing and decay of many cellular transcripts. In the yeast nucleus, the ubiquitous 10-subunit exosome core complex (Exo-9–Rrp44) functions with four conserved cofactors (Rrp6, Rrp47, Mtr4, and Mpp6). Biochemical and structural studies to date have shed insights into the mechanisms of the exosome core and its nuclear cofactors, with the exception of Mpp6. We report the 3.2-Å resolution crystal structure of a S. cerevisiae Exo-9–Mpp6 complex, revealing how linear motifs in the Mpp6 middle domain bind Rrp40 via evolutionary conserved residues. In particular, Mpp6 binds near a tryptophan residue of Rrp40 that is mutated in human patients suffering from pontocerebellar hypoplasia. Using biochemical assays, we show that Mpp6 is required for the ability of Mtr4 to extend the trajectory of an RNA entering the exosome core, suggesting that it promotes the channeling of substrates from the nuclear helicase to the processive RNase. Graphical Abstract Highlights • Yeast Mpp6 is stably bound to the nuclear exosome core both in vivo and in vitro • The Mpp6 middle domain binds the Rrp40 exosome subunit with conserved interactions • Mpp6 enhances the ability of the Mtr4 helicase to channel RNA into the exosome core • The pontocerebellar W238R mutation in human EXOSC3 affects the hMPP6-binding site Falk et al. provide insights into the structure and function of the nuclear RNA exosome. The authors elucidate how the nuclear cofactor Mpp6 is recruited to the exosome core complex and show that it facilitates the threading of RNA substrates from the Mtr4 helicase to the Rrp44 RNase. |
| Databáze: | OpenAIRE |
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