A functional human Poly(A) site requires only a potent DSE and an A-rich upstream sequence

Nuno Miguel Nunes, Wencheng Li, Bin Tian, André Furger

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

We have analysed the sequences required for cleavage and polyadenylation in the intronless melanocortin 4 receptor (MC4R) pre-mRNA. Unlike other intronless genes, 3′end processing of the MC4R primary transcript is independent of any auxiliary sequence elements and only requires the core poly(A) sequences. Mutation of the AUUAAA hexamer had little effect on MC4R 3′end processing but small changes in the short DSE severely reduced cleavage efficiency. The MC4R poly(A) site requires only the DSE and an A-rich upstream sequence to direct efficient cleavage and polyadenylation. Our observation may be highly relevant for the understanding of how human noncanonical poly(A) sites are recognised. This is supported by a genome-wide analysis of over 10 000 poly(A) sites where we show that many human noncanonical poly(A) signals contain A-rich upstream sequences and tend to have a higher frequency of U and GU nucleotides in their DSE compared with canonical poly(A) signals. The importance of A-rich elements for noncanonical poly(A) site recognition was confirmed by mutational analysis of the human JUNB gene, which contains an A-rich noncanonical poly(A) signal.

Original languageEnglish (US)
Pages (from-to)1523-1536
Number of pages14
JournalEMBO Journal
Volume29
Issue number9
DOIs
StatePublished - May 1 2010

Fingerprint

Poly A
Receptor, Melanocortin, Type 4
Polyadenylation
Genes
RNA Precursors
Processing
Nucleotides
Observation
Genome
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Molecular Biology
  • Neuroscience(all)

Keywords

  • 3'end processing
  • Intronless genes
  • Melanocortin 4 receptor
  • Noncanonical poly(A) sites

Cite this

Nunes, Nuno Miguel ; Li, Wencheng ; Tian, Bin ; Furger, André. / A functional human Poly(A) site requires only a potent DSE and an A-rich upstream sequence. In: EMBO Journal. 2010 ; Vol. 29, No. 9. pp. 1523-1536.
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A functional human Poly(A) site requires only a potent DSE and an A-rich upstream sequence. / Nunes, Nuno Miguel; Li, Wencheng; Tian, Bin; Furger, André.

In: EMBO Journal, Vol. 29, No. 9, 01.05.2010, p. 1523-1536.

Research output: Contribution to journalArticle

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