title: hnRNPs and ELAVL1 cooperate with uORFs to inhibit protein translation.
abstract: Most of our knowledge about translation regulatory mechanisms comes from studies on lower organisms. However, the translation control system of higher organisms is less understood. Here we find that in 5' untranslated region (5'UTR) of human Annexin II receptor (AXIIR) mRNA, there are two upstream open reading frames (uORFs) acting in a fail-safe manner to inhibit the translation from the main AUG. These uORFs are unfavorable for re-initiation after termination of uORF translation. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), hnRNPA0 and ELAV like RNA binding protein 1 (ELAVL1) bind to the 5'UTR of AXIIR mRNA. They focus the translation of uORFs on uORF1 and attenuate leaky scanning that bypasses uORFs. The cooperation between the two uORFs and the three proteins formed a multiple fail-safe system that tightly inhibits the translation of downstream AXIIR. Such cooperation between multiple molecules and elements reflects that higher organism develops a complex translation regulatory system to achieve accurate and flexible gene expression control.
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Jiewen
authors: J
authors: Zhang
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Lijuan
authors: L
authors: Kong
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Sichao
authors: S
authors: Guo
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Mengmeng
authors: M
authors: Bu
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Qian
authors: Q
authors: Guo
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Yuan
authors: Y
authors: Xiong
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Ning
authors: N
authors: Zhu
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Chuan
authors: C
authors: Qiu
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Xuejing
authors: X
authors: Yan
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Qian
authors: Q
authors: Chen
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Hongfei
authors: H
authors: Zhang
authors: Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, China.
authors: Junling
authors: J
authors: Zhuang
authors: Department of Cardiology, Xi Jing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Qiong
authors: Q
authors: Wang
authors: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PN 17033, USA.
authors: Samuel S
authors: SS
authors: Zhang
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors: Yan
authors: Y
authors: Shen
authors: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China chenmeihong@hotmail.com.
authors: Meihong
authors: M
authors: Chen