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
[1]   tRNA splicing [J].
Abelson, J ;
Trotta, CR ;
Li, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (21) :12685-12688
[2]   PARTICIPATION OF THE INTRON IN THE REACTION CATALYZED BY THE XENOPUS TRANSFER-RNA SPLICING ENDONUCLEASE [J].
BALDI, MI ;
MATTOCCIA, E ;
BUFARDECI, E ;
FABBRI, S ;
TOCCHINIVALENTINI, GP .
SCIENCE, 1992, 255 (5050) :1404-1408
[3]   BINDING AND CLEAVAGE OF PRE-TRANSFER RNA BY THE XENOPUS SPLICING ENDONUCLEASE - 2 SEPARABLE STEPS OF THE INTRON EXCISION REACTION [J].
BALDI, MI ;
MATTOCCIA, E ;
CIAFRE, S ;
ATTARDI, DG ;
TOCCHINIVALENTINI, GP .
CELL, 1986, 47 (06) :965-971
[4]   Another bridge between kingdoms: tRNA splicing in archaea and eukaryotes [J].
Belfort, M ;
Weiner, A .
CELL, 1997, 89 (07) :1003-1006
[5]   Prediction of a common fold for all four subunits of the yeast tRNA splicing endonuclease: implications for the evolution of the EndA/Sen family [J].
Bujnicki, JM ;
Rychlewski, L .
FEBS LETTERS, 2000, 486 (03) :328-329
[6]   Strange bedfellows: polyadenylation factors at the promoter [J].
Calvo, O ;
Manley, JL .
GENES & DEVELOPMENT, 2003, 17 (11) :1321-1327
[7]   THE SUBNUCLEAR LOCALIZATION OF TRANSFER-RNA LIGASE IN YEAST [J].
CLARK, MW ;
ABELSON, J .
JOURNAL OF CELL BIOLOGY, 1987, 105 (04) :1515-1526
[8]   A 2'-phosphotransferase implicated in tRNA splicing is essential in Saccharomyces cerevisiae [J].
Culver, GM ;
McCraith, SM ;
Consaul, SA ;
Stanford, DR ;
Phizicky, EM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (20) :13203-13210
[9]   Human pre-mRNA cleavage factor IIm contains homologs of yeast proteins and bridges two other cleavage factors [J].
de Vries, H ;
Rüegsegger, U ;
Hübner, W ;
Friedlein, A ;
Langen, H ;
Keller, W .
EMBO JOURNAL, 2000, 19 (21) :5895-5904
[10]   TRANSCRIPTION AND PROCESSING OF CLONED YEAST TYROSINE TRANSFER-RNA GENES MICROINJECTED INTO FROG OOCYTES [J].
DEROBERTIS, EM ;
OLSON, MV .
NATURE, 1979, 278 (5700) :137-143