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#polyadenylation signal

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Processing of mRNA, rRNA, tRNA

Poly(A) signal sequence is

Polyadenylation signal in nascent messenger RNA consists of highly conserved hexamer AAUAAA located ten to thirty nucleotides upstream of CA dinucleotide cleavage site. Recognized by WDR33 and CPSF30 subunits of cleavage and polyadenylation specificity factor CPSF through base stacking in zinc finger pockets. Mutation of AAUAAA to AAGAAA drastically reduces cleavage efficiency and causes read-through transcription. Auxiliary upstream sequence elements USE enriched in uridine and downstream GU-rich downstream sequence element DSE bound by CstF enhance recognition. Identical DNA motif is AATAAA.

Ref: Berg et al., Biochemistry, 9th ed., Chapter 28: Poly(A) signal AAUAAA; Lodish 9th ed., CPSF recognition of AAUAAA hexamer

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Transcription in Eukaryotes

Polyadenylation signal in eukaryotic mRNA is

Eukaryotic pre-mRNAs contain conserved hexamer AAUAAA twenty to thirty nucleotides upstream of cleavage site, transcribed into RNA as polyadenylation signal essential for three prime end formation. Cleavage and polyadenylation specificity factor CPSF binds AAUAAA via WDR33 and CPSF30 zinc fingers recognizing sequence via base stacking interactions, while cleavage stimulation factor CstF binds downstream GU-rich downstream sequence element. Polyadenylation factors CFI, CFII, and endonuclease CPSF73 catalyze endonucleolytic cut. Signal AAUAAA is essential: single point mutation drastically reduces processing. Similar DNA sequence AATAAA in coding strand is classic Hogness box.

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 10: Polyadenylation signal AAUAAA recognition by CPSF; Alberts 7th ed., 3' end formation signals

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