Uncovering a mammalian neural-specific poly(A) binding protein with unique properties

被引:2
|
作者
Sharma, Sahil [1 ]
Kajjo, Sam [1 ]
Harra, Zineb [1 ]
Hasaj, Benedeta [1 ]
Delisle, Victoria [1 ]
Ray, Debashish [2 ]
Gutierrez, Rodrigo L. [1 ]
Carrier, Isabelle [1 ]
Kleinman, Claudia [1 ,3 ]
Morris, Quaid [4 ]
Hughes, Timothy R. [2 ,5 ]
Mcinnes, Roderick [1 ,3 ]
Fabian, Marc R. [1 ,6 ,7 ]
机构
[1] Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada
[2] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada
[3] McGill Univ, Dept Human Genet, Montreal, PQ H3A 0G4, Canada
[4] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA
[5] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada
[6] McGill Univ, Dept Biochem, Montreal, PQ H3A 0G4, Canada
[7] McGill Univ, Dept Oncol, Montreal, PQ H3A 0G4, Canada
基金
加拿大自然科学与工程研究理事会; 美国国家卫生研究院; 加拿大健康研究院;
关键词
RNA binding protein; mRNA translation; poly(A) binding protein; TRANSLATION INITIATION-FACTOR; INDUCIBLE POLY(A)-BINDING PROTEIN; MESSENGER-RNA DEADENYLATION; DENDRITIC BC1 RNA; NEURONAL BC1; REPEATING STRUCTURE; COMPLEX; SEQUENCE; TAIL; PABP;
D O I
10.1101/gad.350597.123
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In this study, Sharma et al. describe a novel cytoplasmic poly(A) binding protein, neuPABP, specifically found in postnatal brain neurons undergoing synaptogenesis. Unlike other PABPs, neuPABP does not bind eIF4G to support mRNA translation; instead, neuPABP interacts with neuron-specific, noncoding RNA BC1, as well as select ribosomal and mitochondrial mRNAs, in free ribonucleoprotein complexes, suggesting a role for neuPABP in suppressing their translation. The mRNA 3 ' poly(A) tail plays a critical role in regulating both mRNA translation and turnover. It is bound by the cytoplasmic poly(A) binding protein (PABPC), an evolutionarily conserved protein that can interact with translation factors and mRNA decay machineries to regulate gene expression. Mammalian PABPC1, the prototypical PABPC, is expressed in most tissues and interacts with eukaryotic translation initiation factor 4G (eIF4G) to stimulate translation in specific contexts. In this study, we uncovered a new mammalian PABPC, which we named neural PABP (neuPABP), as it is predominantly expressed in the brain. neuPABP maintains a unique architecture as compared with other PABPCs, containing only two RNA recognition motifs (RRMs) and maintaining a unique N-terminal domain of unknown function. neuPABP expression is activated in neurons as they mature during synaptogenesis, where neuPABP localizes to the soma and postsynaptic densities. neuPABP interacts with the noncoding RNA BC1, as well as mRNAs coding for ribosomal and mitochondrial proteins. However, in contrast to PABPC1, neuPABP does not associate with actively translating mRNAs in the brain. In keeping with this, we show that neuPABP has evolved such that it does not bind eIF4G and as a result fails to support protein synthesis in vitro. Taken together, these results indicate that mammals have expanded their PABPC repertoire in the brain and propose that neuPABP may support the translational repression of select mRNAs.
引用
收藏
页码:760 / 777
页数:18
相关论文
共 50 条
  • [41] A multifunctional RNA recognition motif in poly(A)-specific ribonuclease with cap and poly(A) binding properties
    Nilsson, Per
    Henriksson, Niklas
    Niedzwiecka, Anna
    Balatsos, Nikolaos A. A.
    Kokkoris, Kyriakos
    Eriksson, Jens
    Virtanen, Anders
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (45) : 32902 - 32911
  • [42] IDENTIFICATION OF SPECIFIC POLYSOMAL POLY(A) BINDING-PROTEINS BY PROTEIN BLOTTING
    SEIDEL, BL
    JACOB, ST
    JOURNAL OF CELL BIOLOGY, 1983, 97 (05): : A352 - A352
  • [43] NFB1 is a neural-specific F-Box protein that interacts with p19(Skp1).
    Erhardt, JA
    Hynicka, WP
    Shen, N
    Stone, NL
    Pittman, RN
    MOLECULAR BIOLOGY OF THE CELL, 1997, 8 : 817 - 817
  • [44] Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning
    Peterson, Kevin A.
    Nishi, Yuichi
    Ma, Wenxiu
    Vedenko, Anastasia
    Shokri, Leila
    Zhang, Xiaoxiao
    McFarlane, Matthew
    Baizabal, Jose-Manuel
    Junker, Jan Philipp
    van Oudenaarden, Alexander
    Mikkelsen, Tarjei
    Bernstein, Bradley E.
    Bailey, Timothy L.
    Bulyk, Martha L.
    Wong, Wing H.
    McMahon, Andrew P.
    GENES & DEVELOPMENT, 2012, 26 (24) : 2802 - 2816
  • [45] EVIDENCE THAT THE POLY(A)-SPECIFIC MESSENGER-RNA BINDING-PROTEIN IS RELATED TO POLY(A) POLYMERASE
    ROSE, KM
    KUMAR, A
    JACOB, ST
    FEDERATION PROCEEDINGS, 1979, 38 (03) : 300 - 300
  • [46] POLY(A) POLYMERASE AND POLY(A)-SPECIFIC MESSENGER-RNA BINDING-PROTEIN ARE ANTIGENICALLY RELATED
    ROSE, KM
    JACOB, ST
    KUMAR, A
    NATURE, 1979, 279 (5710) : 260 - 262
  • [47] P-57 IS A NEURAL SPECIFIC CALMODULIN-BINDING PROTEIN
    CIMLER, BM
    ANDREASEN, TJ
    ANDREASEN, KI
    STORM, DR
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1985, 260 (19) : 784 - 788
  • [48] GZ, A GUANINE NUCLEOTIDE-BINDING PROTEIN WITH UNIQUE BIOCHEMICAL-PROPERTIES
    CASEY, PJ
    FONG, HKW
    SIMON, MI
    GILMAN, AG
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1990, 265 (04) : 2383 - 2390
  • [49] A novel role of the mammalian GSPT/eRF3 associating with poly(A)-binding protein in cap/poly(A)-dependent translation
    Uchida, N
    Hoshino, S
    Imataka, H
    Sonenberg, N
    Katada, T
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (52) : 50286 - 50292
  • [50] Unique Physical Properties and Interactions of the Domains of Methylated DNA Binding Protein 2
    Ghosh, Rajarshi P.
    Nikitina, Tatiana
    Horowitz-Scherer, Rachel A.
    Gierasch, Lila M.
    Uversky, Vladimir N.
    Hite, Kristopher
    Hansen, Jeffrey C.
    Woodcock, Christopher L.
    BIOCHEMISTRY, 2010, 49 (20) : 4395 - 4410