Discrimination among multiple AATAAA sequences correlates with inter-species conservation of select 3' untranslated nucleotides

The DNA sequence corresponding to the 1.3 kb 3' untranslated region of the 6.5 kb human procoilagen α1(IV) mRNA was determined and compared with the mouse sequence obtained from 3' cDNA and genomic clones overlapping the reported 5' half (Oberbaumer et al., 1985, Eur. J. Biochem. 147:217). Although four AAUAAA hexanucleotides are found In the human and seven 1n the mouse RNAs, Northern blot hybridization showed almost exclusive utilization of the most 3' sequence, in contrast to the pattern seen when using αl(I), α2(I), αl(III) and α2(V) procollagen probes. Moreover, the ninety nucleotides 5' to the poly A tall 1n the major αl(IV) mRNAs exhibit a much greater degree of interspecies homology than those encompassing the other three shared AAUAAA recognition signals. Further examination of this highly conserved area revealed the presence of two “consensus sequences” found 1n the 3' noncoding region of a number of RNA polymerase II transcribed genes (Mattaj and Zeller, 1983, Embo J. 2:1883) and, unexpectedly, some similarity with the nucleotides 5' to the poly A attachment signals 1n other procollagen mRNAs.