UAUG and uORFs in human and rodent 5′untranslated mRNAs

被引：192

作者：

Iacono, M

Mignone, F

Pesole, G

机构：

[1] Univ Milan, Dipartimento Sci Biomol & Biotecnol, I-20133 Milan, Italy

[2] CNR, Ist Tecnol Biomed, Sez Bioinformat & Genom, I-70126 Bari, Italy

来源：

GENE | 2005年 / 349卷

关键词：

mRNA translation; post-transcriptional regulation; scanning model; ribosome shunting;

D O I：

10.1016/j.gene.2004.11.041

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The control of translation is a fundamental mechanism in the regulation of gene expression. Among the cis-acting elements that play a role in translation regulation are upstream open reading frames (uORFs) and upstream AUG (uAUGs) located in the 5UTR of mRNAs. We present here a genome-wide analysis of uAUGs and uORFs in a curated set of human and rodent mRNAs. Our study shows that the occurrence of uAUGs is suppressed more strongly than that of uORFs and that in-frame uAUGs are more strongly suppressed than out-of-frame uAUGs. A very similar pattern of uAUG/uORF frequency was also observed in mouse mRNAs. The analysis of orthologous 5UTR sequences revealed a remarkable degree of evolutionary conservation only of those uORFs which acquired some functional activity. Our data suggest that besides leaky scanning and reinitiation, which likely occur with variable and gene-specific efficiency, the ribosome-shunt mechanism, eventually coupled to reinitiation after uORF translation, may be a widespread mode of translation regulation in eukaryotes. (c) 2004 Elsevier B.V. All rights reserved.

引用

收藏

页码：97 / 105

页数：9

相关论文

共 40 条

[1] Role of two upstream open reading frames in the translational control of oncogene mdm2 [J].

Brown, CY ;

Mize, GJ ;

Pineda, M ;

George, DL ;

Morris, DR .

ONCOGENE, 1999, 18 (41) :5631-5637

[2] Translational control of SCL-isoform expression in hematopoietic lineage choice [J].

Calkhoven, CF ;

Müller, C ;

Martin, R ;

Krosl, G ;

Hoang, T ;

Leutz, A .

GENES & DEVELOPMENT, 2003, 17 (08) :959-964

[3] mRNA 5′ region sequence incompleteness:: a potential source of systematic errors in translation initiation codon assignment in human mRNAs [J].

Casadei, R ;

Strippoli, P ;

D'Addabbo, P ;

Canaider, S ;

Lenzi, L ;

Vitale, L ;

Giannone, S ;

Frabetti, F ;

Facchin, F ;

Carinci, P ;

Zannotti, M .

GENE, 2003, 321 :185-193

[4] CSTminer:: a web tool for the identification of coding and noncoding conserved sequence tags through cross-species genome comparison [J].

Castrignanò, T ;

Canali, A ;

Grillo, G ;

Liuni, S ;

Mignone, F ;

Pesole, G .

NUCLEIC ACIDS RESEARCH, 2004, 32 :W624-W627

[5] Translational control by an upstream open reading frame in the HER-2/neu transcript [J].

Child, SJ ;

Miller, MK ;

Geballe, AP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (34) :24335-24341

[6] CART classification of human 5′ UTR sequences [J].

Davuluri, RV ;

Suzuki, Y ;

Sugano, S ;

Zhang, MQ .

GENOME RESEARCH, 2000, 10 (11) :1807-1816

[7] Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2α phosphorylation and translation of a small upstream open reading frame [J].

Fernandez, J ;

Yaman, I ;

Merrick, WC ;

Koromilas, A ;

Wek, RC ;

Sood, R ;

Hensold, J ;

Hatzoglou, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (03) :2050-2058

[8] Cell cycle-dependent translation of p27 involves a responsive element in its 5′-UTR that overlaps with a uORF [J].

Göpfert, U ;

Kullmann, M ;

Hengst, L .

HUMAN MOLECULAR GENETICS, 2003, 12 (14) :1767-1779

[9] A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation [J].

Griffin, E ;

Re, A ;

Hamel, N ;

Fu, CZ ;

Bush, H ;

McCaffrey, T ;

Asch, AS .

NATURE MEDICINE, 2001, 7 (07) :840-846

[10] Regulated translation initiation controls stress-induced gene expression in mammalian cells [J].

Harding, HP ;

Novoa, I ;

Zhang, YH ;

Zeng, HQ ;

Wek, R ;

Schapira, M ;

Ron, D .

MOLECULAR CELL, 2000, 6 (05) :1099-1108

← 1 2 3 4 →