RNA cargoes associating with in cellular functioning in Fmrl Fmr1 reveal deficits null mice

被引:392
作者
Miyashiro, KY
Beckel-Mitchener, A
Purk, TP
Becker, KG
Barret, T
Liu, L
Carbonetto, S
Weiler, IJ
Greenough, WT
Eberwine, J [1 ]
机构
[1] Univ Penn, Sch Med, Dept Pharmacol, Dept Psychiat, Philadelphia, PA 19104 USA
[2] McGill Univ, Dept Neurol & Neurosurg, Neurosci Res Ctr, Montreal, PQ H3A 2B4, Canada
[3] Univ Illinois, WM Keck Ctr Comparat & Funct Genomics, Urbana, IL 61801 USA
[4] NIA, DNA Array Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA
[5] Univ Illinois, Beckman Inst, Dept Psychol, Dept Psychiat,Neurosci Program, Urbana, IL 61801 USA
关键词
D O I
10.1016/S0896-6273(03)00034-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The Fragile X mental retardation-1 (Fmr1) gene encodes a multifunctional protein, FMRP, with intrinsic RNA binding activity. We have developed an approach, antibody-positioned RNA amplification (APRA), to identify the RNA cargoes associated with the in vivo configured FMRP messenger ribonucleoprotein (mRNP) complex. Using APRA as a primary screen, putative FMRP RNA cargoes were assayed for their ability to bind directly to FMRP using traditional methods of assessing RNA-protein interactions, including UV-crosslinking and filter binding assays. Approximately 60% of the APRA-defined mRNAs directly associate with FMRP. By examining a subset of these mRNAs and their encoded proteins in brain tissue from Fmr1 knockout mice, we have observed that some of these cargoes as well as the proteins they encode show discrete changes in abundance and/or differential subcellular distribution. These data are consistent with spatially selective regulation of multiple biological pathways by FMRP.
引用
收藏
页码:417 / 431
页数:15
相关论文
共 58 条
  • [1] FMR1 PROTEIN - CONSERVED RNP FAMILY DOMAINS AND SELECTIVE RNA-BINDING
    ASHLEY, CT
    WILKINSON, KD
    REINES, D
    WARREN, ST
    [J]. SCIENCE, 1993, 262 (5133) : 563 - 566
  • [2] A 33-KDA POLYPEPTIDE WITH HOMOLOGY TO THE LAMININ RECEPTOR - COMPONENT OF TRANSLATION MACHINERY
    AUTH, D
    BRAWERMAN, G
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) : 4368 - 4372
  • [3] BAKKER CE, 1994, CELL, V78, P23
  • [4] A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein
    Bardoni, B
    Schenck, A
    Mandel, JL
    [J]. HUMAN MOLECULAR GENETICS, 1999, 8 (13) : 2557 - 2566
  • [5] Analysis of domains affecting intracellular localization of the FMRP protein
    Bardoni, B
    Sittler, A
    Shen, Y
    Mandel, JL
    [J]. NEUROBIOLOGY OF DISEASE, 1997, 4 (05) : 329 - 336
  • [6] Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein
    Brown, V
    Small, K
    Lakkis, L
    Feng, Y
    Gunter, C
    Wilkinson, KD
    Warren, ST
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (25) : 15521 - 15527
  • [7] Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome
    Brown, V
    Jin, P
    Ceman, S
    Darnell, JC
    O'Donnell, WT
    Tenenbaum, SA
    Jin, XK
    Feng, Y
    Wilkinson, KD
    Keene, JD
    Darnell, RB
    Warren, ST
    [J]. CELL, 2001, 107 (04) : 477 - 487
  • [8] HIPPOCAMPAL COMMISSURAL CONNECTIONS IN THE NEONATAL RAT
    BUCHHALTER, JR
    FIELES, A
    DICHTER, MA
    [J]. DEVELOPMENTAL BRAIN RESEARCH, 1990, 56 (02): : 211 - 216
  • [9] Ceman S, 1999, MOL CELL BIOL, V19, P7925
  • [10] Identification of mouse YB1/p50 as a component of the FMRP-associated mRNP particle
    Ceman, S
    Nelson, R
    Warren, ST
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 279 (03) : 904 - 908