Suppression of the 5′ splice site mutation in the nagase analbuminemic rat with mutated U1snRNA

被引:10
作者
Hitomi, Y [1 ]
Sugiyama, K [1 ]
Esumi, H [1 ]
机构
[1] Natl Canc Ctr, Res Inst E, Invest Treatment Div, Chiba 277, Japan
关键词
D O I
10.1006/bbrc.1998.9406
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
Nagase analbuminemic rats (NAR) are deficient in serum albumin due to skipping of the albumin exon H caused by a mutation in the intron HI. This mutation deletes nucleotides from +5 to +11 in the 5' splice site region, where it interacts with U1snRNA. To determine whether the mutation can be suppressed by the compensatory base substitution in U1snRNA, we constructed mutated U1snRNA genes with various degrees of complementarity to the mutated 5' splice site. Several mutated U1snRNA genes activated the mutated 5' splice site of the intron HI, when cotransfected with the albumin minigene derived from NAR. In vivo activity of these mutated U1snRNAs correlated well with the predicted thermodynamic stability. Since mutation in the 5' splice site is one of common causes of genetic defects in human (5), these data indicate that NAR is a good model system to examine the possibility of gene therapy using a mutated U1snRNA. (C) 1998 Academic Press.
引用
收藏
页码:11 / 16
页数:6
相关论文
共 29 条
[1]  
BLACK DL, 1995, RNA, V1, P763
[2]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[3]   U1 SMALL NUCLEAR RNAS WITH ALTERED SPECIFICITY CAN BE STABLY EXPRESSED IN MAMMALIAN-CELLS AND PROMOTE PERMANENT CHANGES IN PREMESSENGER RNA SPLICING [J].
COHEN, JB ;
BROZ, SD ;
LEVINSON, AD .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (05) :2666-2676
[4]   SUPPRESSION OF MAMMALIAN 5' SPLICE-SITE DEFECTS BY U1 SMALL NUCLEAR RNAS FROM A DISTANCE [J].
COHEN, JB ;
SNOW, JE ;
SPENCER, SD ;
LEVINSON, AD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (22) :10470-10474
[5]   A U6 SNRNA-PRE-MESSENGER-RNA INTERACTION CAN BE RATE-LIMITING FOR U1-INDEPENDENT SPLICING [J].
CRISPINO, JD ;
SHARP, PA .
GENES & DEVELOPMENT, 1995, 9 (18) :2314-2323
[6]   A 7-BASE-PAIR DELETION IN AN INTRON OF THE ALBUMIN GENE OF ANALBUMINEMIC RATS [J].
ESUMI, H ;
TAKAHASHI, Y ;
SATO, S ;
NAGASE, S ;
SUGIMURA, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (01) :95-99
[7]   PRESENCE OF ALBUMIN MESSENGER-RNA PRECURSORS IN NUCLEI OF ANALBUMINEMIC RAT-LIVER LACKING CYTOPLASMIC ALBUMIN MESSENGER-RNA [J].
ESUMI, H ;
TAKAHASHI, Y ;
SEKIYA, T ;
SATO, S ;
NAGASE, S ;
SUGIMURA, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (03) :734-738
[8]   IMPROVED FREE-ENERGY PARAMETERS FOR PREDICTIONS OF RNA DUPLEX STABILITY [J].
FREIER, SM ;
KIERZEK, R ;
JAEGER, JA ;
SUGIMOTO, N ;
CARUTHERS, MH ;
NEILSON, T ;
TURNER, DH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (24) :9373-9377
[9]   BIOCHEMICAL-MECHANISMS OF CONSTITUTIVE AND REGULATED PRE-MESSENGER-RNA SPLICING [J].
GREEN, MR .
ANNUAL REVIEW OF CELL BIOLOGY, 1991, 7 :559-599
[10]   PROPERTIES OF A U1/MESSENGER-RNA 5' SPLICE SITE DUPLEX CONTAINING PSEUDOURIDINE AS MEASURED BY THERMODYNAMIC AND NMR METHODS [J].
HALL, KB ;
MCLAUGHLIN, LW .
BIOCHEMISTRY, 1991, 30 (07) :1795-1801