5xjq › Citations

Negative cooperativity between Gemin2 and RNA provides insights into RNA selection and the SMN complex's release in snRNP assembly.

Figure 1.
Figure 2.
Figure 3.
Yi H, Mu L, Shen C, Kong X, Wang Y, Hou Y, Zhang R
OpenAccess logo Nucleic Acids Res 48 895-911 (2020)
Related entries: 5xjr, 5xjs

Cited: 5 times
EuropePMC logo PMID: 31799625

Abstract

The assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around the nonameric Sm site of snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA). How the SMN complex assembles snRNP cores is largely unknown, especially how the SMN complex achieves high RNA assembly specificity and how it is released. Here we show, using crystallographic and biochemical approaches, that Gemin2 of the SMN complex enhances RNA specificity of SmD1/D2/F/E/G via a negative cooperativity between Gemin2 and RNA in binding SmD1/D2/F/E/G. Gemin2, independent of its N-tail, constrains the horseshoe-shaped SmD1/D2/F/E/G from outside in a physiologically relevant, narrow state, enabling high RNA specificity. Moreover, the assembly of RNAs inside widens SmD1/D2/F/E/G, causes the release of Gemin2/SMN allosterically and allows SmD3/B to join. The assembly of SmD3/B further facilitates the release of Gemin2/SMN. This is the first to show negative cooperativity in snRNP assembly, which provides insights into RNA selection and the SMN complex's release. These findings reveal a basic mechanism of snRNP core assembly and facilitate pathogenesis studies of SMA.

Articles - 5xjq mentioned but not cited (1)

  1. Negative cooperativity between Gemin2 and RNA provides insights into RNA selection and the SMN complex's release in snRNP assembly. Yi H, Mu L, Shen C, Kong X, Wang Y, Hou Y, Zhang R. Nucleic Acids Res 48 895-911 (2020)


Reviews citing this publication (2)

  1. Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities. Blijlevens M, Li J, van Beusechem VW. Int J Mol Sci 22 5110 (2021)
  2. The SMN Complex at the Crossroad between RNA Metabolism and Neurodegeneration. Faravelli I, Riboldi GM, Rinchetti P, Lotti F. Int J Mol Sci 24 2247 (2023)

Articles citing this publication (2)

  1. In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome. Yang XC, Desotell A, Lin MH, Paige AS, Malinowska A, Sun Y, Aik WS, Dadlez M, Tong L, Dominski Z. RNA 29 1673-1690 (2023)
  2. Mechanism of assembly of snRNP cores assisted by ICln and the SMN complex in fission yeast. Hu Y, Hou Y, Zhou S, Wang Y, Shen C, Mu L, Su D, Zhang R. iScience 26 107604 (2023)


Quick links