Negative Cooperativity between Gemin2 and RNA provides Insights into RNA Selection and the SMN Complex’s Release in snRNP Assembly

Abstract

The assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. The deficiency of SMN causes neurodegenerative disease spinal muscular atrophy (SMA). How the SMN complex assembles snRNP cores in the second phase is largely unknown, especially how the SMN complex achieves stringent RNA specificity, ensuring seven Sm proteins assemble only around snRNAs, by requiring an extra 3'-adjacent stem-loop (SL) in addition to a nonameric Sm site RNA (PuAUUUNUGPu) on which snRNP cores can spontaneously form without chaperons in vitro. Moreover, how the SMN complex is released from snRNP cores is unknown.