Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)

被引:123
作者
Lanz, RB [1 ]
Razani, B [1 ]
Goldberg, AD [1 ]
O'Malley, BW [1 ]
机构
[1] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词
D O I
10.1073/pnas.192571399
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Steroid receptor RNA activator (SRA) is an RNA transcript that functions as a eukaryotic transcriptional coactivator for steroid hormone receptors. We report here the isolation and functional characterization of distinct RNA substructures within the SRA molecule that constitute its coactivation function. We used comparative sequence analysis and free energy calculations to systematically study SRA RNA subdomains for identification of structured regions and base pairings, and we used site-directed mutagenesis to assess their functional consequences. Together with genetic deletion analysis, this approach identified six RNA motifs in SRA important for coactivation. Because all nucleotide changes in the mutants that disrupted SRA function were silent mutations presumed not to alter deduced encoded amino acid sequence, our analysis provides strong evidence that SRA-mediated coactivation is executed by distinct RNA motifs and not by an encoded protein.
引用
收藏
页码:16081 / 16086
页数:6
相关论文
共 26 条
  • [1] alpha helix-RNA major groove recognition in an HIV-1 Rev peptide RRE RNA complex
    Battiste, JL
    Mao, HY
    Rao, NS
    Tan, RY
    Muhandiram, DR
    Kay, LE
    Frankel, AD
    Williamson, JR
    [J]. SCIENCE, 1996, 273 (5281) : 1547 - 1551
  • [2] Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERα transcriptional activity and MCF-7 proliferation
    Cavarretta, ITR
    Mukopadhyay, R
    Lonard, DM
    Cowsert, LM
    Bennett, CF
    O'Malley, BW
    Smith, CL
    [J]. MOLECULAR ENDOCRINOLOGY, 2002, 16 (02) : 253 - 270
  • [3] AN INTERACTIVE FRAMEWORK FOR RNA SECONDARY STRUCTURE PREDICTION WITH A DYNAMICAL TREATMENT OF CONSTRAINTS
    GASPIN, C
    WESTHOF, E
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1995, 254 (02) : 163 - 174
  • [4] Glass CK, 2000, GENE DEV, V14, P121
  • [5] IMPROVED PREDICTIONS OF SECONDARY STRUCTURES FOR RNA
    JAEGER, JA
    TURNER, DH
    ZUKER, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) : 7706 - 7710
  • [6] PATTERN-ANALYSIS OF RNA SECONDARY STRUCTURE - SIMILARITY AND CONSENSUS OF MINIMAL-ENERGY FOLDING
    KONINGS, DAM
    HOGEWEG, P
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1989, 207 (03) : 597 - 614
  • [7] KONINGS DAM, 1995, RNA, V1, P559
  • [8] A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex
    Lanz, RB
    McKenna, NJ
    Onate, SA
    Albrecht, U
    Wong, JM
    Tsai, SY
    Tsai, MJ
    O'Malley, BW
    [J]. CELL, 1999, 97 (01) : 17 - 27
  • [9] PREDICTING COMMON FOLDINGS OF HOMOLOGOUS RNAS
    LE, SY
    ZUKER, M
    [J]. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 1991, 8 (05) : 1027 - 1044
  • [10] THE NUCLEAR RECEPTOR SUPERFAMILY - THE 2ND DECADE
    MANGELSDORF, DJ
    THUMMEL, C
    BEATO, M
    HERRLICH, P
    SCHUTZ, G
    UMESONO, K
    BLUMBERG, B
    KASTNER, P
    MARK, M
    CHAMBON, P
    EVANS, RM
    [J]. CELL, 1995, 83 (06) : 835 - 839