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

被引：74

作者：

Nunes, Nuno Miguel ^{[1
]}

Li, Wencheng ^{[2
]}

Tian, Bin ^{[2
]}

Furger, Andre ^{[1
]}

机构：

[1] Univ Oxford, Lab Genes & Dev, Dept Biochem, Oxford OX1 3QU, England

[2] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA

来源：

EMBO JOURNAL | 2010年 / 29卷 / 09期

基金：

英国惠康基金;

关键词：

3 ' end processing; intronless genes; melanocortin; 4; receptor; noncanonical poly(A) sites; MESSENGER-RNA POLYADENYLATION; CLEAVAGE STIMULATION FACTOR; B-CELL DIFFERENTIATION; 3' END FORMATION; MALE GERM-CELLS; FACTOR CSTF-64; POINT MUTATIONS; DNA-DAMAGE; ELEMENTS; 3'-END;

D O I：

10.1038/emboj.2010.42

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. The EMBO Journal (2010) 29, 1523-1536. doi:10.1038/emboj.2010.42; Published online 25 March 2010

引用

页码：1523 / 1536

页数：14

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