A unique mechanism of snRNP core assembly.

The assembly of most spliceosomal snRNP cores involves seven Sm proteins (D1/D2/F/E/G/D3/B) forming a ring around snRNA, typically requiring essential assembly chaperones like the SMN complex, associated with spinal muscular atrophy (SMA). Strikingly, in budding yeast, snRNP core assembly only involves Brr1, a nonessential homolog of Gemin2. Here, we reveal two distinct pathways in budding yeast: an inefficient chaperone-mediated pathway involving Brr1 and a novel factor, Lot5, and a direct pathway. Lot5 binds D1/D2/F/E/G to form a heterohexameric ring (6S). Brr1 binds D1/D2/F/E/G and 6S but cannot displace Lot5 to facilitate assembly. Disruption of BRR1 and LOT5 genes caused mild growth retardation, but LOT5 overexpression substantially impeded growth. The direct pathway uniquely involves F/E/G as a trimer and a stable D1/D2/F/E/G intermediate complex, explaining the non-essentiality of chaperones. These findings unveil a unique snRNP core assembly mechanism, illuminate the evolution of assembly chaperones, and suggest avenues for studying SMA pathophysiology.