The zipper model of translational control: A small upstream ORF is the switch that controls structural remodeling of an mRNA leader

被引：175

作者：

Yaman, I

Fernandez, J

Liu, HY

Caprara, M

Komar, AA

Koromilas, AE

Zhou, LY

Snider, MD

Scheuner, D

Kaufman, RJ

Hatzoglou, M ^{[1
]}

机构：

[1] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA

[2] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Sch Med, Ctr RNA Mol Biol, Cleveland, OH 44106 USA

[4] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada

[5] Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada

[6] Univ Michigan, Med Ctr, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

来源：

CELL | 2003年 / 113卷 / 04期

关键词：

D O I：

10.1016/S0092-8674(03)00345-3

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：

Transport of the essential amino acids arginine and lysine is critical for the survival of mammalian cells. The adaptive response to nutritional stress involves increased translation of the arginine/lysine transporter (cat-1) mRNA via an internal ribosome entry site (IRES) within the mRNA leader. Induction of cat-1 IRES activity requires both translation of a small upstream open reading frame (uORF) within the IRES and phosphorylation of the translation initiation factor eIF2alpha. We show here that translation of the upstream ORF unfolds an inhibitory structure in the mRNA leader, eliciting a conformational change that yields an active IRES. The IRES, whose activity is induced by amino acid starvation, is created by RNA-RNA interactions between the 5' end of the leader and downstream sequences. This study suggests that the structure of the IRES is dynamic and regulation of this RNA structure is a mechanism of translational control.

引用

页码：519 / 531

页数：13

共 23 条

[1] IRESdb:: the internal ribosome entry site database [J].