Identification of a Human Endonuclease Complex Reveals a Link between tRNA Splicing and Pre-mRNA 3′ End Formation

Identification of a Human Endonuclease Complex Reveals a Link between tRNA Splicing and Pre-mRNA 3′ End Formation

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 cha...

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Bibliographic Details
Published in:Cell Vol. 117; no. 3; pp. 311 - 321
Main Authors: Paushkin, Sergey V, Patel, Meenal, Furia, Bansri S, Peltz, Stuart W, Trotta, Christopher R
Format: Journal Article
Language:English
Published: United States Elsevier Inc 30-04-2004
Subjects:
Amino Acid Sequence
Cell Line
Cell Nucleolus - chemistry
Cell Nucleolus - metabolism
Cell Nucleus - chemistry
Cell Nucleus - metabolism
Consensus Sequence
Conserved Sequence
Endonucleases - chemistry
Endonucleases - isolation & purification
Endonucleases - metabolism
Endoribonucleases - metabolism
HeLa Cells
Humans
Introns
Isoenzymes - chemistry
Isoenzymes - genetics
Isoenzymes - metabolism
Molecular Sequence Data
Protein Subunits
RNA Precursors - genetics
RNA Precursors - metabolism
RNA Processing, Post-Transcriptional
RNA Splicing
RNA, Small Interfering - metabolism
RNA, Transfer - chemistry
RNA, Transfer - metabolism
Saccharomyces cerevisiae - enzymology
Sequence Homology, Amino Acid
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Summary: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-mRNA 3′ 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 RNAprocessing events.
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ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(04)00342-3