메뉴 건너뛰기




Volumn 303, Issue 5656, 2004, Pages 383-387

RNA Leaching of Transcription Factors Disrupts Transcription in Myotonic Dystrophy

Author keywords

[No Author keywords available]

Indexed keywords

DISEASES; ENZYMES; GENES; MUTAGENESIS;

EID: 0346373752     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1088679     Document Type: Article
Times cited : (134)

References (34)
  • 1
    • 0026566108 scopus 로고
    • J. D. Brook et al., Cell 68, 799 (1992).
    • (1992) Cell , vol.68 , pp. 799
    • Brook, J.D.1
  • 11
    • 0347584003 scopus 로고    scopus 로고
    • note
    • Appropriate conditions for in vitro binding are insufficiently understood to replicate the selectivity of the TF binding process that occurs in vivo (Fig. 1). We observe only nonselective binding of purified TF in vitro with all RNAs, whether mutant RNA or heterologous unrelated RNAs (12). The same discordance can be inferred for conditions used for CUGBP binding in vitro (31) that fail to reproduce the selectivity for mutant versus wild-type RNA that is evident in vivo (4, 12), (Fig. 1A).
  • 12
    • 0347584001 scopus 로고    scopus 로고
    • unpublished observations
    • A. Ebralidze et al., unpublished observations.
    • Ebralidze, A.1
  • 15
    • 0347584002 scopus 로고    scopus 로고
    • note
    • GI: 479168 (32) with Matinspector V2.2 software (33).
  • 17
    • 0347583999 scopus 로고    scopus 로고
    • note
    • Experimental details are available as supporting material on Science Online.
  • 19
    • 0348213714 scopus 로고    scopus 로고
    • note
    • Although mutant RNA double-strand hairpins of CUG-repeat domains have been noted in vitro by electron microscopy, and binding of CUGBP in vitro at their single-strand junctions (31), in vitro binding studies may be vulnerable to overinterpretation for the in vivo setting [compare note (11)]. In vivo mutant RNP extracted from cells has yet to be studied structurally in this fashion.
  • 20
    • 0346952960 scopus 로고    scopus 로고
    • note
    • We apply the same standard of 30% change for "significantly" disturbed transcription as used in the HD study (24).
  • 21
    • 0348213715 scopus 로고    scopus 로고
    • note
    • Seven additional genes were recently studied, of which three were significantly suppressed and four unchanged in mutant RNA-expressing cells. A total of nine genes have now been tested with TF "restorations." When Sp1 or Sp3 was overexpressed, full or partial recovery was seen in three out of four of the depressed genes, with the fourth presumably responding to depleted TFs not tested, by this model. In contrast, among the five genes that were unchanged in mutant RNA-expressing cells, none (0/5) was stimulated by TF overexpression.
  • 22
    • 0037150687 scopus 로고    scopus 로고
    • A. W. Dunah et al., Science 296, 2238 (2002).
    • (2002) Science , vol.296 , pp. 2238
    • Dunah, A.W.1
  • 27
    • 0034646516 scopus 로고    scopus 로고
    • F. Le Page et al., Cell 101, 159 (2000).
    • (2000) Cell , vol.101 , pp. 159
    • Le Page, F.1
  • 34
    • 0347584000 scopus 로고    scopus 로고
    • note
    • We acknowledge the many collegial interactions with C. Thornton and T. Cooper, who supplied information, materials and advice that assisted many phases of the project. Supported by grants to R.P.J. from the Muscular Dystrophy Association and of the National Institute for Arthritis, Muscle, and Skin Diseases (NIAMS) of the NIH.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.