translation agency

The poly(A)-limiting element is a conserved cis-acting sequence that regulates poly(A) tail length on nuclear pre-mRNAs.
Gu H; Das Gupta J; Schoenberg DR; Department of Pharmacology, Ohio State
November 30, 1999
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8943-8. Unique Identifier :

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.

JOURNAL ARTICLE Animal Base Sequence Carrier Proteins/GENETICS Cell Nucleus/METABOLISM DNA-Binding Proteins/GENETICS Genomic Library Human HIV-1/GENETICS Interleukin-2/*GENETICS Jurkat Cells L Cells (Cell Line) Mice Molecular Sequence Data Poly A/CHEMISTRY/GENETICS Recombinant Proteins/BIOSYNTHESIS RNA Precursors/*GENETICS RNA, Messenger/*CHEMISTRY/*GENETICS Sequence Deletion Support, U.S. Gov't, P.H.S. Transfection Transferrin/*GENETICS Zinc Fingers