Interconversion and mechanisms between Lsm-type and Sm-type heteroheptameric rings: implications for spliceosome evolution and RNA metabolism

Eukaryotes harbor both Sm-type and Lsm-type heteroheptameric rings, which are essential in RNA metabolism. Despite their similar subunits and evolutionary ties, they interact with RNA in distinct ways, functioning as scaffolds and chaperones, respectively. However, the mechanistic basis of their evolutionary divergence remains unclear. Using the Sm ring (D1-D2-F-E-G-D3-B) and the Lsm2-8 ring, both of which form the cores of distinct spliceosomal snRNPs, as model systems, we investigated the feasibility and mechanisms of their interconversion. We found that the interactions among subcomplexes (SCs) 1-3 in the Sm ring (D1/D2, F/E/G, and D3/B) differ from those in Lsm2-8 (Lsm2/3, Lsm6/5/7, and Lsm8/4), implying the formation of distinct assembly intermediates. By strengthening the SC1-SC3 interaction, we achieved the conversion of the Sm ring into an Lsm-type ring. Conversely, increasing the SC2-SC3 affinity did not yield a successful conversion. Furthermore, by weakening the SC1-SC3 interaction and introducing mutations in the RNA-binding regions of SC1 and SC2, we converted Lsm2-8 into a Sm-type ring. These findings provide mechanistic insights into how similar protein components can assemble into functionally distinct heteroheptameric rings, a principle likely applicable to Lsm1-7 and the U7 snRNP core, and offer deep insights into spliceosome and eukaryotic evolution.