(A) Model of tandem hnRNP C RRM interaction with hnRNP A1 at the 3′ splice site (ss). (1) Regulatory elements surrounding the intron/exon boundary. The 3′ ss is delimited by a conserved cAG/G site preceded by a polypyrimidine tract (PPT) of 10–15 nt (Senapathy et al. 1990). (2) Two interacting RRMs of hnRNP C recognize the PPT. At the exon boundary, the hnRNP A1 RRMs recognizing the YAGG motif would interact with the neighboring hnRNP C RRM, anchoring it to the 3′ end of the PPT. Depending on the relative position of the spliced exon with respect to the hnRNP C tetramer, the exon would be either enhanced or silenced. (B) Model of unr IRES activation by hnRNP C through binding site competition and displacement of PTB. (1) Localization of polypyrimidine tracts (PPT) within human unr 5′ UTR. (2) PTB was shown to bind PPTs within the unr IRES, repressing translation initiation. Binding to the PPT sites in cyan was confirmed experimentally (Cornelis et al. 2005); green PPTs are putative binding sites. Since these PPTs occur on both sides of the start codon, the binding of PTB would prevent the assembly of translation machinery. (3) HnRNP C tetramer displaces PTB at the beginning of mitosis. Its two confirmed poly(U) binding sites (overlapping with the PTB sites in cyan) are localized upstream of the start site (Schepens et al. 2007). The binding of hnRNP C and removal of PTB would therefore expose the start site for translation.
