Two distinct SECIS structures capable of directing selenocysteine incorporation in eukaryotes

被引:119
作者
Grundner-Culemann, E [1 ]
Martin, GW [1 ]
Harney, JW [1 ]
Berry, MJ [1 ]
机构
[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Thyroid Div, Boston, MA 02115 USA
关键词
3 ' untranslated region; recoding; RNA structure; translation;
D O I
10.1017/S1355838299981542
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
Translation of UGA as selenocysteine requires specific RNA secondary structures in the mRNAs of selenoproteins. These elements differ in sequence, structure, and location in the mRNA, that is, coding versus 3' untranslated region, in prokaryotes, eukaryotes, and archaea. Analyses of eukaryotic selenocysteine insertion Sequence (SECIS) elements via computer folding programs, mutagenesis studies, and chemical and enzymatic probing has led to the derivation of a predicted consensus structural model for these elements. This model consists of a stem-loop or hairpin, with conserved nucleotides in the loop and in a non-Watson-Crick motif at the base of the stem. However, the sequences of a number of SECIS elements predict that they would diverge from the consensus structure in the loop region. Using site-directed mutagenesis to introduce mutations predicted to either disrupt or restore structure, or to manipulate loop size or stem length, we show that eukaryotic SECIS elements fall into two distinct classes, termed forms 1 and 2. Form 2 elements have additional secondary structures not present in form 1 elements. By either insertion or deletion of the sequences and structures distinguishing the two classes of elements while maintaining appropriate loop size, conversion of a form 1 element to a functional form P-like element and of a form 2 to a functional form 1-like element was achieved. These results suggest commonality of function of the two classes. The information obtained regarding the existence of two classes of SECIS elements and the tolerances for manipulations of stem length and loop size should facilitate designing RNA molecules for obtaining high-resolution structural information about these elements.
引用
收藏
页码:625 / 635
页数:11
相关论文
共 16 条
[1]  
BERRY MJ, 1991, J BIOL CHEM, V266, P14155
[2]   FUNCTIONAL-CHARACTERIZATION OF THE EUKARYOTIC SECIS ELEMENTS WHICH DIRECT SELENOCYSTEINE INSERTION AT UGA CODONS [J].
BERRY, MJ ;
BANU, L ;
HARNEY, JW ;
LARSEN, PR .
EMBO JOURNAL, 1993, 12 (08) :3315-3322
[3]   RECOGNITION OF UGA AS A SELENOCYSTEINE CODON IN TYPE-I DEIODINASE REQUIRES SEQUENCES IN THE 3' UNTRANSLATED REGION [J].
BERRY, MJ ;
BANU, L ;
CHEN, Y ;
MANDEL, SJ ;
KIEFFER, JD ;
HARNEY, JW ;
LARSEN, PR .
NATURE, 1991, 353 (6341) :273-276
[4]   TIGHT CONTROL OF GENE-EXPRESSION IN MAMMALIAN-CELLS BY TETRACYCLINE-RESPONSIVE PROMOTERS [J].
GOSSEN, M ;
BUJARD, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5547-5551
[5]   A protein binds the selenocysteine insertion element in the 3'-UTR of mammalian selenoprotein mRNAs [J].
Hubert, N ;
Walczak, R ;
Carbon, P ;
Krol, A .
NUCLEIC ACIDS RESEARCH, 1996, 24 (03) :464-469
[6]   Analysis of eukaryotic mRNA structures directing cotranslational incorporation of selenocysteine [J].
Kollmus, H ;
Flohe, L ;
McCarthy, JEG .
NUCLEIC ACIDS RESEARCH, 1996, 24 (07) :1195-1201
[7]   An RNA-binding protein recognizes a mammalian selenocysteine insertion sequence element required for cotranslational incorporation of selenocysteine [J].
Lesoon, A ;
Mehta, A ;
Singh, R ;
Chisolm, GM ;
Driscoll, DM .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (04) :1977-1985
[8]   Knowing when not to stop: Selenocysteine incorporation in eukaryotes [J].
Low, SC ;
Berry, MJ .
TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (06) :203-208
[9]  
Martin GW, 1998, RNA, V4, P65
[10]  
Martin GW, 1996, RNA, V2, P171