FIGURE 10-17 RNA transcribed in the "wrong" direction from most promoters in metazoans has a high frequency of polyadenylation signals and a low frequency of binding sites for U1 snRNA. This pattern may account for the termination of transcription in the "wrong" direction after about 2 kb for most of these transcripts. PAS represents polyadenylation signals encoded in the DNA that are transcribed into RNA. Cleavage of transcripts transcribed in the upstream direction (scissors) is proposed to generate free RNA ends that are digested by the nuclear exosome and a nuclear 5′→3′ exonuclease, XRN1. In contrast, pre-mRNAs synthesized by RNA polymerase II transcribing into coding regions have evolved to have few polyadenylation signals. Where they do occur, these signals are usually preceded by a binding site for U1 snRNP, which inhibits cleavage at a nearby PAS (stop sign). However, the PAS used to generate the 3′ end of an mRNA does not have a closely associated U1 RNP binding site. See A. E. Almada et al., 2013, Nature 499:360.