Several studies have shown that tau immunopurifies with several RNA-binding proteins [41, 42], and recent work has nominated nuclear speckles as a participant in tauopathies through the scaffold protein SRRM2. Lester and colleagues showed that tau deposits purified from model systems, including mice and human cells, contain many RNAs and are highly enriched for small nuclear and small nucleolar RNAs (snRNAs and snoRNAs) [7]. These findings are consistent with previous work showing that tau aggregates in brain are typically RNA-positive [43], and suggest pathological properties for nuclear tau [42, 44–46], as Lester and colleagues speculate pathological tau may be seeded by RNA into nuclear aggregates in human tauopathy disorders. In model systems this may be particularly relevant, as tau truncated species accumulate to high levels in many models, and tau fragments readily relocalize to the nucleus in some cellular systems [47]. Investigation of a small number of human tauopathy cases demonstrated mislocalization of SRRM2 in AD, but did not document the presence of nuclear tau/RNA assemblies [7]. Here, we confirm nuclear clearance and cytoplasmic accumulation of pSRRM2 in a larger
