The function of the NineTeen Complex (NTC) in regulating spliceosome conformations and fidelity during pre-mRNA splicing

Abstract

The NineTeen Complex (NTC) of proteins associates with the spliceosome during pre-mRNA splicing and is essential for both steps of intron removal. The NTC and other NTC-associated proteins are recruited to the spliceosome where they participate in regulating the formation and progression of essential spliceosome conformations required for the two steps of splicing. It is now clear that the NTC is an integral component of active spliceosomes from yeast to humans and provides essential support for the spliceosomal snRNPs (small nuclear ribonucleoproteins). In the present article, we discuss the identification and characterization of the yeast NTC and review recent work in yeast that supports the essential role for this complex in the regulation and fidelity of splicing.

Figure 1

Complexes formed during spliceosome assembly and activation Intron containing pre-mRNAs with 5′SS (5′ splice site), BS (branch site) and 3′SS (3′ splice site) sequences are recognised by the spliceosomal snRNPs during spliceosome assembly and activation. The U1 and U2 snRNPs interact with the 5′SS and BS, respectively, to form complex A. The ATPase Prp28 then allows the U4/U6.U5 tri-snRNP to assemble with the pre-mRNA along with the NTC proteins to form complex B. The GTPase Snu114 and the ATPase Brr2 induce U4/U6 unwinding with subsequent destabilisation of the U1 and U4 snRNPs to form the complex B^ACT. The ATPase Prp2 then remodels the spliceosome to the complex B* which is the catalytically active spliceosome. The action of Cwc25 and Yju2 then induce step 1 of splicing and formation of complex C which contains the step 1 intermediates. Finally the ATPases Prp16 and Prp22 induce step 2 of splicing and formation of the post-splicing complex which contains the spliced mRNA and the removed intron. This post-splicing complex is then disassembled and the snRNPs and NTC proteins are recycled for another round of splicing.