The RNA-binding protein ELAV regulates Hox RNA processing, expression and function within the Drosophila nervous system

被引:25
|
作者
Rogulja-Ortmann, Ana [1 ]
Picao-Osorio, Joao [2 ]
Villava, Casandra [2 ]
Patraquim, Pedro [2 ]
Lafuente, Elvira [2 ]
Aspden, Julie [2 ]
Thomsen, Stefan [2 ]
Technau, Gerhard M. [1 ]
Alonso, Claudio R. [2 ]
机构
[1] Johannes Gutenberg Univ Mainz, Inst Genet, D-55099 Mainz, Germany
[2] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England
来源
DEVELOPMENT | 2014年 / 141卷 / 10期
基金
英国惠康基金;
关键词
Central nervous system; Drosophila; ELAV/Hu; Hox; RNA-binding protein; RNA processing; Alternative polyadenylation (APA); Alternative splicing; Segment-specific apoptosis; POLYMERASE-II; GENE-EXPRESSION; MESSENGER-RNAS; ULTRABITHORAX; MELANOGASTER; NEURONS; FAMILY; MECHANISMS; ELEMENTS; CORD;
D O I
10.1242/dev.101519
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The regulated head-to-tail expression of Hox genes provides a coordinate system for the activation of specific programmes of cell differentiation according to axial level. Recent work indicates that Hox expression can be regulated via RNA processing but the underlying mechanisms and biological significance of this form of regulation remain poorly understood. Here we explore these issues within the developing Drosophila central nervous system (CNS). We show that the pan-neural RNA-binding protein (RBP) ELAV (Hu antigen) regulates the RNA processing patterns of the Hox gene Ultrabithorax (Ubx) within the embryonic CNS. Using a combination of biochemical, genetic and imaging approaches we demonstrate that ELAV binds to discrete elements within Ubx RNAs and that its genetic removal reduces Ubx protein expression in the CNS leading to the respecification of cellular subroutines under Ubx control, thus defining for the first time a specific cellular role of ELAV within the developing CNS. Artificial provision of ELAV in glial cells (a cell type that lacks ELAV) promotes Ubx expression, suggesting that ELAV-dependent regulation might contribute to cell type-specific Hox expression patterns within the CNS. Finally, we note that expression of abdominal A and Abdominal B is reduced in elav mutant embryos, whereas other Hox genes (Antennapedia) are not affected. Based on these results and the evolutionary conservation of ELAV and Hox genes we propose that the modulation of Hox RNA processing by ELAV serves to adapt the morphogenesis of the CNS to axial level by regulating Hox expression and consequently activating local programmes of neural differentiation.
引用
收藏
页码:2046 / 2056
页数:11
相关论文
共 50 条
  • [41] Protein Syndesmos is a novel RNA-binding protein that regulates primary cilia formation
    Avolio, Rosario
    Jarvelin, Aino I.
    Mohammed, Shabaz
    Agliarulo, Ilenia
    Condelli, Valentina
    Zoppoli, Pietro
    Calice, Giovanni
    Sarnataro, Daniela
    Bechara, Elias
    Tartaglia, Gian G.
    Landriscina, Matteo
    Castello, Alfredo
    Esposito, Franca
    Matassa, Danilo S.
    NUCLEIC ACIDS RESEARCH, 2018, 46 (22) : 12067 - 12086
  • [42] Neuronal RNA-binding protein HuD regulates addiction-related gene expression and behavior
    Oliver, R. J.
    Brigman, J. L.
    Bolognani, F.
    Allan, A. M.
    Neisewander, J. L.
    Perrone-Bizzozero, N. I.
    GENES BRAIN AND BEHAVIOR, 2018, 17 (04)
  • [43] Altered translational repression of an RNA-binding protein, Elav by AOA2-causative Senataxin mutation
    Choudhury, Saumitra Dey
    Ancy, V. S.
    Mushtaq, Zeeshan
    Kumar, Vimlesh
    SYNAPSE, 2017, 71 (05)
  • [44] The RNA-binding protein HuD regulates neuronal cell identity and maturation
    Akamatsu, W
    Fujihara, H
    Mitsuhashi, T
    Yano, M
    Shibata, S
    Hayakawa, Y
    Okano, HJ
    Sakakibara, S
    Takano, H
    Takano, T
    Takahashi, T
    Noda, T
    Okano, H
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (12) : 4625 - 4630
  • [45] Transportin 2 Regulates Apoptosis through the RNA-binding Protein HuR
    von Roretz, Christopher
    Macri, Angelo M.
    Gallouzi, Imed-Eddine
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (29) : 25983 - 25991
  • [46] A role of neuronal RNA-binding protein Hu and NF45/90 in the nervous system
    Igarashi, Mania
    Yano, Masato
    Okano, Hirotaka J.
    Okano, Hideyuki
    NEUROSCIENCE RESEARCH, 2008, 61 : S153 - S153
  • [47] RNA-binding protein hnRNPU regulates multiple myeloma resistance to selinexor
    Wang, Xin
    Xu, Juan
    Li, Qun
    Zhang, Yue
    Lin, Zhimei
    Zhai, Xinyu
    Wang, Fangfang
    Huang, Jingcao
    Gao, Qianwen
    Wen, Jingjing
    Li, Linfeng
    Feng, Yu
    Luo, Hongmei
    Li, Qian
    Liu, Xiang
    Li, Junying
    Zhao, Fei
    Zhang, Li
    Niu, Ting
    Sun, Chunyan
    Zheng, Yuhuan
    CANCER LETTERS, 2024, 580
  • [48] The RNA-binding protein, HuD regulates proglucagon biosynthesis in pancreatic α cells
    Ahn, Sojin
    Tak, Hyosun
    Kang, Hoin
    Ryu, Seungyeon
    Jeong, Seung Min
    Kim, Wook
    Lee, Eun Kyung
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2020, 530 (01) : 266 - 272
  • [49] Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
    Silvestri, Beatrice
    Mochi, Michela
    Garone, Maria Giovanna
    Rosa, Alessandro
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (23)
  • [50] Synthetic antibodies as tools to probe RNA-binding protein function
    Laver, John D.
    Ancevicius, Kristin
    Sollazzo, Pietro
    Westwood, J. Timothy
    Sidhu, Sachdev S.
    Lipshitz, Howard D.
    Smibert, Craig A.
    MOLECULAR BIOSYSTEMS, 2012, 8 (06) : 1650 - 1657