From Virus Structure to Spliceosome Function Via RNA Splicing
Structural studies by EM and EM in the frozen-hydrated state, combined with molecular biology, revealed that the endogenous spliceosome is composed of four native spliceosomes, each similar to the test-tube spliceosome, which are connected by the pre-mRNA, hence termed supraspliceosome (Sperling et al 2008; R. Sperling 2017). Importantly, the entire repertoire of nuclear pre-mRNAs is assembled in splicing-active supraspliceosomes. A remarkable feature of supraspliceosomes is that they individually package a single pre-mRNA transcript of different size and number of introns into complexes of a unique structure, indicating their universal nature. This multi-subunit complex also regulates alternative splicing, and harbors components of all the pre-mRNA processing activities. Thus, the supraspliceosome is a stand-alone complete macromolecular machine capable of performing splicing, alternative splicing, and encompass all the nuclear processing activities that the pre-mRNA has to undergo before it can exit from the nucleus to the cytoplasm to encode for proteins.