The poly(A)-limiting element is a conserved cis-acting sequence that regulates poly(A) tail length on nuclear pre-mRNAs.
Most vertebrate mRNAs exit the nucleus with a 200+-residue poly(A) tail and are deadenylated to yield heterogeneous polymers of 50-200 adenosine residues on any given mRNA. We previously reported that Xenopus albumin mRNA and pre-mRNA have an unusually short, discrete 17-residue poly(A) tail and showed that regulation of poly(A) length is controlled independently by two cis-acting poly(A)-limiting elements (PLE A and PLE B) located in the terminal exon. The present study sought to determine the generality of this regulatory mechanism. Transferrin mRNA also has a discrete <20-nt poly(A) tail, and deletion mapping experiments identified an element homologous to the albumin gene PLE B within the terminal exon of the transferrin gene that conferred poly(A) length regulation on a globin reporter mRNA. Based on this similarity the PLE B sequence was used in a database search to identify candidate mRNA targets for regulated polyadenylation. Of the several hundred sequences identified in this manner we focused on HIV-EP2/Schnurri-2, a member of a family of genes encoding related zinc finger transcription factors. A striking feature of the PLE-like element in these genes is its location 10-33 bp upstream of the translation stop codon. We demonstrate that HIV-EP2 mRNA has a <20-nt poly(A) tail, for which the identified PLE-like sequence is responsible. These results indicate that the presence of a PLE can predict mRNAs with <20-nt poly(A) tails, and that nuclear regulation of poly(A) tail length is a feature of many mRNAs.
Gu
H
H
Department of Pharmacology, Ohio State Biochemistry Program, and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Das Gupta
J
J
Schoenberg
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DR
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D015698:Genomic Library; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D019169:Jurkat Cells; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D011061:Poly A / Q000737:chemistry / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D014157:Transcription Factors; D014162:Transfection; D014168:Transferrin / Q000235:genetics*; D016335:Zinc Fingers
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D012322:RNA Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D014168:Transferrin; C077171:HIVEP2 protein, human; D011061:Poly A