PMID- 27789685 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200615 IS - 1362-4962 (Electronic) IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 45 IP - 5 DP - 2017 Mar TI - hnRNPs and ELAVL1 cooperate with uORFs to inhibit protein translation. PG - 2849-2864 LID - gkw991 [pii] LID - 10.1093/nar/gkw991 [doi] AB - 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. CI - (c) The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. FAU - Zhang, Jiewen AU - Zhang J AD - 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. FAU - Kong, Lijuan AU - Kong L AD - 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. FAU - Guo, Sichao AU - Guo S AD - 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. FAU - Bu, Mengmeng AU - Bu M AD - 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. FAU - Guo, Qian AU - Guo Q AD - 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. FAU - Xiong, Yuan AU - Xiong Y AD - 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. FAU - Zhu, Ning AU - Zhu N AD - 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. FAU - Qiu, Chuan AU - Qiu C AD - 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. FAU - Yan, Xuejing AU - Yan X AD - 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. FAU - Chen, Qian AU - Chen Q AD - 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. FAU - Zhang, Hongfei AU - Zhang H AD - 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. FAU - Zhuang, Junling AU - Zhuang J AD - Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, China. FAU - Wang, Qiong AU - Wang Q AD - Department of Cardiology, Xi Jing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China. FAU - Zhang, Samuel S AU - Zhang SS AD - Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PN 17033, USA. FAU - Shen, Yan AU - Shen Y AD - 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. FAU - Chen, Meihong AU - Chen M AD - 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. LA - eng PT - Journal Article DEP - 20161026 PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 PMC - PMC5389705 EDAT- 2016/10/30 06:00 MHDA- 2016/10/30 06:01 PMCR- 2016/10/26 CRDT- 2016/10/30 06:00 PHST- 2016/10/23 00:00 [accepted] PHST- 2015/10/06 00:00 [received] PHST- 2016/10/30 06:00 [pubmed] PHST- 2016/10/30 06:01 [medline] PHST- 2016/10/30 06:00 [entrez] PHST- 2016/10/26 00:00 [pmc-release] AID - gkw991 [pii] AID - 10.1093/nar/gkw991 [doi] PST - ppublish SO - Nucleic Acids Res. 2017 Mar;45(5):2849-2864. doi: 10.1093/nar/gkw991. Epub 2016 Oct 26.