Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 publication

DOI

10.1038/emboj.2010.42

Type

Journal article

Journal

EMBO J

Publication Date

05/05/2010

Volume

29

Pages

1523 - 1536

Keywords

3' Flanking Region, 3' Untranslated Regions, Adenosine, Antigens, Neoplasm, Base Sequence, Cell Line, DNA-Binding Proteins, Humans, Molecular Sequence Data, Mutation, Neoplasm Proteins, Poly A, Proto-Oncogene Proteins c-jun, RNA Precursors, Receptor, Melanocortin, Type 4, Uridine