<p>Binding of intact U1 snRNPs to three cryptic 5′ splice sites (labeled with A, B, C) within intron 7 of the U1-70K pre-mRNA (middle) activates an alternative 3′ splice site. Inclusion of the alternative exon 7a introduces a premature termination codon (stop sign) into the mature U1-70K mRNA, which is degraded by nonsense-mediated decay (NMD; following the pathway upwards). Reduced U1-70K mRNA and protein levels result in a co-depletion of U1C protein; thus, U1 snRNPs are assembled inefficiently. U1C/U1-70K-deficient U1 snRNPs are unable to activate the alternative 3′ splice site, therefore, constitutive U1-70K splicing is enhanced, and more functional U1-70K mRNA and protein are produced (following the pathway downwards). Normal U1 snRNP assembly is restored and alternative 3′ splice site activation can occur again to close the regulatory circle (for a detailed description, see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003856#s3" target="_blank"><i>Discussion</i></a>).</p
