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The poly(A)-limiting element is a conserved cis-acting sequence that regulates poly(A) tail length on nuclear
H Gu1, J Das Gupta, D R Schoenberg
1Department of Pharmacology, Ohio State Biochemistry Program, and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Summary
This study reveals that specific DNA sequences, known as poly(A)-limiting elements (PLEs), control short poly(A) tail lengths in mRNAs like transferrin and HIV-EP2. This mechanism, previously observed in Xenopus, is more widespread than initially thought.
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Processing
Background:
- Vertebrate mRNAs typically have long poly(A) tails (50-200 nt) after deadenylation.
- Previously, Xenopus albumin mRNA was found to have a short, discrete 17-nt poly(A) tail regulated by poly(A)-limiting elements (PLEs).
Purpose of the Study:
- To investigate the generality of the PLE-mediated poly(A) tail length regulation mechanism.
- To identify other mRNAs regulated by this mechanism and the responsible cis-acting elements.
Main Methods:
- Deletion mapping experiments were used to identify regulatory elements in transferrin mRNA.
- Database searches utilizing the PLE B sequence identified candidate mRNA targets.
- Reporter assays and sequence analysis were performed on HIV-EP2/Schnurri-2.
Main Results:
- Transferrin mRNA also possesses a discrete poly(A) tail (<20 nt) regulated by a PLE B-homologous element.
- A PLE-like element was identified upstream of the stop codon in HIV-EP2/Schnurri-2, responsible for its <20-nt poly(A) tail.
- The presence of a PLE sequence can predict mRNAs with short poly(A) tails.
Conclusions:
- Nuclear regulation of poly(A) tail length by PLEs is a common mechanism across various mRNAs.
- This regulatory mechanism extends beyond Xenopus and impacts genes like transferrin and HIV-EP2.