Nucleic Acids Research, 1995, Vol. 23, No. 14 2614-2620
© 1995
MOLECULAR BIOLOGY |
Cleavage site determinants min the mammalian polydenylation signal
UMDNJ—New Jersey Medical School, Department of Microbiology and Molecular Genetics 185 South Orange Avenue, Newark, NJ 07103, USA 1Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University Princeton, NJ 08544–1014, USA
*To whom correspondence should be addressed
Received April 28, 1995. Accepted June 7, 1995.
Using a series of position and nucleotide variants of the SV40 late polyadenylation signal we have demonstrated that three sequence elements determine the precise site of 3'-end cleavage in mammalian premRNAs: an upstream AAUAAA element, a downstream U-rich element consisting of five nucleotides, at least four of which are uridine, and a nucleotide preference at the site of cleavage in the order A>U> C>> G. Cleavage occurs no closer than 11 bases, but no farther than 23 bases from the AAUAAA element. The downstream U-rich element is usually located 10–30 bases from the cleavage site. The relative position of the AAUAAA and the U-rich elements define the approximate region within a 13 base domain in which cleavage will occur. The exact position of cleavage Is then determined by the local nucleotide sequence In the order of preference noted above. This model accounts for nearly three quarters of olyadenylation signals surveyed and is consistent with previous experimental observations.
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