Identification of a human endonuclease complex reveals a link between tRNA splicing and Pre-mRNA 3′ end formation

被引:196
作者
Paushkin, SV [1 ]
Patel, M [1 ]
Furia, BS [1 ]
Peltz, SW [1 ]
Trotta, CR [1 ]
机构
[1] PTC Therapeut, S Plainfield, NJ 07080 USA
关键词
D O I
10.1016/S0092-8674(04)00342-3
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
tRNA splicing is a fundamental process required for cell growth and division. The first step in tRNA splicing is the removal of introns catalyzed in yeast by the tRNA splicing endonuclease. The enzyme responsible for intron removal in mammalian cells is unknown. We present the identification and characterization of the human tRNA splicing endonuclease. This enzyme consists of HsSen2, HsSen34, HsSen15, and HsSen54, homologs of the yeast tRNA endonuclease subunits. Additionally, we identified an alternatively spliced isoform of SEN2 that is part of a complex with unique RNA endonuclease activity. Surprisingly, both human endonuclease complexes are associated with pre-mRNA3' end processing factors. Furthermore, siRNA-mediated depletion of SEN2 exhibited defects in maturation of both pre-tRNA and pre-mRNA. These findings demonstrate a link between pre-tRNA splicing and pre-mRNA 3' end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events.
引用
收藏
页码:311 / 321
页数:11
相关论文
共 45 条
[31]  
RAUHUT R, 1990, J BIOL CHEM, V265, P18180
[32]   Perspective: Prostate cancer susceptibility genes [J].
Simard, J ;
Dumont, M ;
Soucy, P ;
Labrie, F .
ENDOCRINOLOGY, 2002, 143 (06) :2029-2040
[33]   YEAST TRANSFER RNA3LEU GENE TRANSCRIBED AND SPLICED IN A HELA-CELL EXTRACT [J].
STANDRING, DN ;
VENEGAS, A ;
RUTTER, WJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (10) :5963-5967
[34]   Complex protein interactions within the human polyadenylation machinery identify a novel component [J].
Takagaki, Y ;
Manley, JL .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (05) :1515-1525
[35]   A candidate prostate cancer susceptibility gene encodes tRNA 3′ processing endoribonuclease [J].
Takaku, H ;
Minagawa, A ;
Takagi, M ;
Nashimoto, M .
NUCLEIC ACIDS RESEARCH, 2003, 31 (09) :2272-2278
[36]   A candidate prostate cancer susceptibility gene at chromosome 17p [J].
Tavtigian, SV ;
Simard, J ;
Teng, DHF ;
Abtin, V ;
Baumgard, M ;
Beck, A ;
Camp, NJ ;
Carillo, AR ;
Chen, Y ;
Dayananth, P ;
Desrochers, M ;
Dumont, M ;
Farnham, JM ;
Frank, D ;
Frye, C ;
Ghaffari, S ;
Gupte, JS ;
Hu, R ;
Iliev, D ;
Janecki, T ;
Kort, EN ;
Laity, KE ;
Leavitt, A ;
Leblanc, G ;
McArthur-Morrison, J ;
Pederson, A ;
Penn, B ;
Peterson, KT ;
Reid, JE ;
Richards, S ;
Schroeder, M ;
Smith, R ;
Snyder, SC ;
Swedlund, B ;
Swensen, J ;
Thomas, A ;
Tranchant, M ;
Woodland, AM ;
Labrie, F ;
Skolnick, MH ;
Neuhausen, S ;
Rommens, J ;
Cannon-Albright, LA .
NATURE GENETICS, 2001, 27 (02) :172-180
[37]   The yeast tRNA splicing endonuclease: A tetrameric enzyme with two active site subunits homologous to the archaeal tRNA endonucleases [J].
Trotta, CR ;
Miao, F ;
Arn, EA ;
Stevens, SW ;
Ho, CK ;
Rauhut, R ;
Abelson, JN .
CELL, 1997, 89 (06) :849-858
[38]  
TROTTA CR, 1998, RNA WORLD, V2, P561
[39]   3′-End processing of pre-mRNA in eukaryotes [J].
Wahle, E ;
Rüegsegger, U .
FEMS MICROBIOLOGY REVIEWS, 1999, 23 (03) :277-295
[40]   Two distinct forms of the 64,000 Mr protein of the cleavage stimulation factor are expressed in mouse male germ cells [J].
Wallace, AM ;
Dass, B ;
Ravnik, SE ;
Tonk, V ;
Jenkins, NA ;
Gilbert, DJ ;
Copeland, NG ;
MacDonald, CC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :6763-6768