| Structural highlights
Function
[GEMI5_HUMAN] The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. GEMIN5 acts as the snRNA-binding protein of the SMN complex.[1] [2] [3]
Publication Abstract from PubMed
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 or m7G 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.
Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly.,Xu C, Ishikawa H, Izumikawa K, Li L, He H, Nobe Y, Yamauchi Y, Shahjee HM, Wu XH, Yu YT, Isobe T, Takahashi N, Min J Genes Dev. 2016 Nov 1;30(21):2376-2390. Epub 2016 Nov 10. PMID:27881600[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G. Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. J Biol Chem. 2002 Feb 15;277(7):5631-6. Epub 2001 Nov 19. PMID:11714716 doi:http://dx.doi.org/10.1074/jbc.M109448200
- ↑ Battle DJ, Lau CK, Wan L, Deng H, Lotti F, Dreyfuss G. The Gemin5 protein of the SMN complex identifies snRNAs. Mol Cell. 2006 Jul 21;23(2):273-9. PMID:16857593 doi:http://dx.doi.org/S1097-2765(06)00378-9
- ↑ Chari A, Golas MM, Klingenhager M, Neuenkirchen N, Sander B, Englbrecht C, Sickmann A, Stark H, Fischer U. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell. 2008 Oct 31;135(3):497-509. doi: 10.1016/j.cell.2008.09.020. PMID:18984161 doi:http://dx.doi.org/10.1016/j.cell.2008.09.020
- ↑ Xu C, Ishikawa H, Izumikawa K, Li L, He H, Nobe Y, Yamauchi Y, Shahjee HM, Wu XH, Yu YT, Isobe T, Takahashi N, Min J. Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly. Genes Dev. 2016 Nov 1;30(21):2376-2390. Epub 2016 Nov 10. PMID:27881600 doi:http://dx.doi.org/10.1101/gad.288340.116
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