CUG repeats present in myotonin kinase RNA form metastable "slippery" hairpins

被引:134
作者
Napierala, M [1 ]
Krzyzosiak, WJ [1 ]
机构
[1] Polish Acad Sci, Inst Bioorgan Chem, Canc Genet Lab, PL-61704 Poznan, Poland
关键词
D O I
10.1074/jbc.272.49.31079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We show that CUG repeats form "slippery" hairpins in their natural sequence context of the myotonin kinase gene transcript. This novel type of RNA structure is characterized by strong S-1 and T-1 nuclease and lead cleavages in the terminal loop and by mild lead cleavages in the hairpin stem. The latter effect indicates a relaxed metastable structure of the stem. (CUG)(5) repeats do not form any detectable secondary structure, whereas hairpins of increasing stability are formed by (CUG)(11), (CUG)(21), and (CUG)(49). The potential role of the RNA hairpin structure in the pathogenesis of myotonic dystrophy is discussed.
引用
收藏
页码:31079 / 31085
页数:7
相关论文
共 38 条
  • [1] STRUCTURE OF AN RNA DOUBLE HELIX INCLUDING URACIL-URACIL BASE-PAIRS IN AN INTERNAL LOOP
    BAEYENS, KJ
    DEBONDT, HL
    HOLBROOK, SR
    [J]. NATURE STRUCTURAL BIOLOGY, 1995, 2 (01): : 56 - 62
  • [2] Identification of two nuclear proteins which bind to RNA CUG repeats: Significance for myotonic dystrophy
    Bhagwati, S
    Ghatpande, A
    Leung, B
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 228 (01) : 55 - 62
  • [3] MOLECULAR-BASIS OF MYOTONIC-DYSTROPHY - EXPANSION OF A TRINUCLEOTIDE (CTG) REPEAT AT THE 3' END OF A TRANSCRIPT ENCODING A PROTEIN-KINASE FAMILY MEMBER
    BROOK, JD
    MCCURRACH, ME
    HARLEY, HG
    BUCKLER, AJ
    CHURCH, D
    ABURATANI, H
    HUNTER, K
    STANTON, VP
    THIRION, JP
    HUDSON, T
    SOHN, R
    ZEMELMAN, B
    SNELL, RG
    RUNDLE, SA
    CROW, S
    DAVIES, J
    SHELBOURNE, P
    BUXTON, J
    JONES, C
    JUVONEN, V
    JOHNSON, K
    HARPER, PS
    SHAW, DJ
    HOUSMAN, DE
    [J]. CELL, 1992, 68 (04) : 799 - 808
  • [4] PB(II)-CATALYSED CLEAVAGE OF THE SUGAR-PHOSPHATE BACKBONE OF YEAST TRANSFER RNAPHE - IMPLICATIONS FOR LEAD TOXICITY AND SELF-SPLICING RNA
    BROWN, RS
    HINGERTY, BE
    DEWAN, JC
    KLUG, A
    [J]. NATURE, 1983, 303 (5917) : 543 - 546
  • [5] CRYSTALLOGRAPHIC AND BIOCHEMICAL INVESTIGATION OF THE LEAD(II)-CATALYZED HYDROLYSIS OF YEAST PHENYLALANINE TRANSFER-RNA
    BROWN, RS
    DEWAN, JC
    KLUG, A
    [J]. BIOCHEMISTRY, 1985, 24 (18) : 4785 - 4801
  • [6] STRUCTURAL-ANALYSIS OF 3 PROKARYOTIC 5S RIBOSOMAL-RNA SPECIES AND SELECTED 5S RIBOSOMAL-RNA RIBOSOMAL-PROTEIN COMPLEXES BY MEANS OF PB(II)-INDUCED HYDROLYSIS
    CIESIOLKA, J
    LORENZ, S
    ERDMANN, VA
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 204 (02): : 575 - 581
  • [7] AN UNSTABLE TRIPLET REPEAT IN A GENE RELATED TO MYOTONIC MUSCULAR-DYSTROPHY
    FU, YH
    PIZZUTI, A
    FENWICK, RG
    KING, J
    RAJNARAYAN, S
    DUNNE, PW
    DUBEL, J
    NASSER, GA
    ASHIZAWA, T
    DEJONG, P
    WIERINGA, B
    KORNELUK, R
    PERRYMAN, MB
    EPSTEIN, HF
    CASKEY, CT
    [J]. SCIENCE, 1992, 255 (5049) : 1256 - 1258
  • [8] GACY AM, 1995, CELL, V81, P533
  • [9] USE OF LEAD(II) TO PROBE THE STRUCTURE OF LARGE RNAS - CONFORMATION OF THE 3' TERMINAL DOMAIN OF ESCHERICHIA-COLI 16S RIBOSOMAL-RNA AND ITS INVOLVEMENT IN BUILDING THE TRANSFER-RNA BINDING-SITES
    GORNICKI, P
    BAUDIN, F
    ROMBY, P
    WIEWIOROWSKI, M
    KRYZOSIAK, W
    EBEL, JP
    EHRESMANN, C
    EHRESMANN, B
    [J]. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 1989, 6 (05) : 971 - 984
  • [10] Myotonic dystrophy: Will the real gene please step forward!
    Harris, S
    Moncrieff, C
    Johnson, K
    [J]. HUMAN MOLECULAR GENETICS, 1996, 5 : 1417 - 1423