U4:U5:U6 tri-snRNP complexFormation of the Spliceosomal A complexPoly(A)pb IIYYYYexon 1SR-proteinsU6U2 snRNPsAAGPoly(A) polSF3b14bU4 snRNPPolr2aPoly(A) polymerase alphaAGexon 1YYYYProcessing of Intron-Containing Pre-mRNARnmt (methyltransferase)AU2 snRNPYYYYU5P-Formation of pre-mRNPsmRNA Capping3U4/U6splicing factor SF3BFormation of the active Spliceosomal C complex5Alternative Splicingheterogeneous nuclear ribonucleoproteinsU2AFhnRNP regulatorsAdditional FactorsFormation of the Spliceosomal E complexRNA helicase AU4degradedAGMethylation of mRNAexon 153Note: New participating members shown at each stepFormation of the Spliceosomal A complexGUCstFCF IIACF I5YYYYintronRNA helicase53exon 2Internal methylation of mRNAmRNA splicing (major pathway)Additional FactorsPutative Alternative SplicingU5U1exon 2GMPPiAUG5 G capAGAAAAAAAexon 1U6 snRNPAU2 snRNPYYYYexon 2Cap BindingFormation of the Spliceosomal E complexsnRNP Sm core complexhnRNPspre-mRNAFormation of the Spliceosomal B complex653snRNP Sm core complex355RegulatorsmRNA splice site selectionUG3CFIU2CF IISR-binding sitesAGexon 2U2AFSR-proteinsexon 2exon 15Additional SR proteinsAccessory Proteinsexon 1Internal methylation of mRNA5exon 23Formation of the Spliceosomal C complexSR-binding sitesU5 snRNPAGFormation of the Spliceosomal B complexSR protein kinasesPrimary RNA transcriptSerine/Argenine Rich Proteins(SR)snRNP Sm core complex5AYYYYsplicing factor SF3ASpt5U1 snRNPRegulation of35Poly(A)-binding protein II533Formation of pre-mRNPsU1 snRNPmRNA cappingRNAi pathwayiPo3DDX20rsp-7dnj-30pab-3ptb-1rsp-6cpf-2Rnu6rnp-3RNU2spt-5rsp-1prp-8tag-72U1 snRNASF3B5prp-17SSFA1snr-7CLK1Y59A8B.6Y113G7B.17cpf-1F58B3.7F43G9.5hrp-2C27H5.3HNRPABC36B1.5FUSIP1HNRPA2B1HNRPA1suf-1CLK3him-1snr-6PTBP2METTL3SFRS9PCBP2mog-4phf-5F56D2.6F11A10.2gut-2prp-4Y55F3AM.3C25A1.4nxf-1prp-17lsm-7F28C1.1HNRPH2CSTF2F59A2.4W03F9.10HNRPCSFRS3CLK4U5 snRNAC36B1.5F43G6.5SF4Y48B6A.3Y76B12C.7uaf-1SFRS5T13H5.4cel-1M03C11.7F11A10.8Y73B6BL.33NONOHNRPA3P1SFRS10RBMXbath-43rha-1rsp-3F47G9.1gut-2rsr-1F09G2.4HNRPDsap-1snr-4SNRPNetr-1rnp-2ama-1eft-1F37E3.1prp-21snr-1SF3B4rsp-4mog-5T08A11.2tag-203FNBP3rsp-2TXNL4Ateg-1dcr-1snr-5HRMT1L1rnp-7SFRS14T08B2.5SSFA1SNRPBprp-8SNRPNNCBP2snr-3HNRPKC44B7.2Y67H2A.1unc-75NSEP1mog-1F08G12.2Y55F3BR.1CUGBP2tag-172U4 snRNA