Journal
GENES & DEVELOPMENT
Volume 30, Issue 21, Pages 2376-2390Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.288340.116
Keywords
SMN complex; WD40 domain; X-ray crystal structure
Categories
Funding
- National Cancer Institute [ACB-12002]
- National Institute of General Medical Sciences [AGM-12006]
- DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]
- AbbVie
- Bayer Pharma AG
- BoehringerIngelheim
- Canada Foundation for Innovation
- Eshelman Institute for Innovation
- Genome Canada through the Ontario Genomics Institute
- Innovative Medicines Initiative (European Union/European Federation of Pharmaceutical Industries and Associations) [115766]
- Janssen
- Novartis Pharma AG
- Ontario Ministry of Economic Development and Innovation
- Pfizer
- Sao Paulo Research Foundation (FAPESP)
- Takeda
- Wellcome Trust
- National Nature Science Foundation of China [31570737]
- Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Agency (JST)
- Chinese Government 1000 Youth Talent Program
- Merck
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In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring complex on pre-snRNAs at the conserved Sm site [ A(U) 4-6G]. Gemin5, a WD40 protein component of the SMN complex, is responsible for recognizing pre-snRNAs. In addition, Gemin5 has been reported to specifically bind to the m7G cap. In this study, we show that the WD40 domain of Gemin5 is both necessary and sufficient for binding the Sm site of pre-snRNAs by isothermal titration calorimetry (ITC) and mutagenesis assays. We further determined the crystal structures of the WD40 domain of Gemin5 in complex with the Sm site orm7G cap of pre-snRNA, which reveal that the WD40 domain of Gemin5 recognizes the Sm site and m7G cap of pre-snRNAs via two distinct binding sites by respective base-specific interactions. In addition, we also uncovered a novel role of Gemin5 in escorting the truncated forms of U1 pre-snRNAs for proper disposal. Overall, the elucidated Gemin5 structures will contribute to a better understanding of Gemin5 in small nuclear ribonucleic protein (snRNP) biogenesis as well as, potentially, other cellular activities.
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