Variant snRNPs: New players within the spliceosome system.

Much evidence is now accumulating that, in addition to their general role in splicing, the components of the core splicing machinery have extensive regulatory potential. In particular, recent evidence has demonstrated that de-regulation of these factors cause the highest extent of alternative splicing changes compared to de-regulation of the classical splicing regulators. This lack of a general inhibition of splicing resonates the differential splicing effects observed in different disease pathologies associated with specific mutations targeting core spliceosomal components. In this review we will summarize what is currently known regarding the involvement of core spliceosomal U-snRNP complexes in perturbed tissue development and human diseases and argue for the existence of a compensatory mechanism enabling cells to cope with drastic perturbations in core splicing components. This system maintains the correct balance of spliceosomal snRNPs through differential expression of variant (v)U-snRNPs.