Alternative titles; symbolstRNA SPLICING ENDONUCLEASE 34, S. CEREVISIAE, HOMOLOG OFLEUKOCYTE RECEPTOR CLUSTER GENE 5; LENG5SEN34, YEAST, HOMOLOG OF; SEN34HGNC Ap...
Alternative titles; symbols
HGNC Approved Gene Symbol: TSEN34
Cytogenetic location: 19q13.42 Genomic coordinates (GRCh38): 19:54,189,969-54,194,531 (from NCBI)
tRNA splicing is a fundamental process required for cell growth and division. SEN34 is a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns, the first step in tRNA splicing (Paushkin et al., 2004).
▼ Cloning and Expression
By searching sequence databases using yeast Sen34 as probe, followed by PCR of human cDNA libraries, Paushkin et al. (2004) isolated a cDNA encoding SEN34. SEN34 contains 315 amino acids. Human and yeast SEN34 are highly homologous, particularly in the active site domain. Immunofluorescence microscopy of transfected HeLa cells localized SEN34 to the nucleus, and it was frequently found in nucleoli in dot-like structures.
▼ Gene Function
Paushkin et al. (2004) identified and characterized the human tRNA splicing endonuclease. This enzyme consists of SEN2 (608753), SEN34, SEN15 (608756), and SEN54 (608755), homologs of the yeast tRNA endonuclease subunits. Additionally, an alternatively spliced variant of SEN2 is part of a complex with unique RNA endonuclease activity. Paushkin et al. (2004) found that both human endonuclease complexes are associated with CLP1 (608757), a pre-mRNA 3-prime end processing factor. Small interfering RNA-mediated depletion of SEN2 led to defects in maturation of both pre-tRNA and pre-mRNA. These findings demonstrated a link between pre-tRNA splicing and pre-mRNA 3-prime end formation, suggesting that the endonuclease subunits function in multiple RNA processing events.
By genomic sequence analysis, Wende et al. (2000) mapped the TSEN34 gene to the leukocyte receptor cluster on chromosome 19q13.4.
▼ Molecular Genetics
Budde et al. (2008) identified a homozygous missense mutation in the TSEN34 gene (R58W; 608754.0001) in a patient of Turkish descent with pontocerebellar hypoplasia type 2 (PCH2C; 612390).
▼ ALLELIC VARIANTS ( 1 Selected Example):
.0001 PONTOCEREBELLAR HYPOPLASIA, TYPE 2C (1 patient)
In a patient of Turkish descent with pontocerebellar hypoplasia type 2 (PCH2C; 612390), Budde et al. (2008) identified a C-to-T transition at nucleotide 172 of the TSEN34 gene, resulting in an arg-to-trp substitution at codon 58 (R58W). Arginine at position 58 is conserved in mammals closely related to humans. Within vertebrates, this position is exchanged by small hydrophobic residues only (isoleucine, leucine). Therefore, exchange for tryptophan at this position may produce steric hindrance. This mutation was not identified in 91 Dutch DNA samples, and only 3 heterozygotes were identified among 139 samples of Turkish origin.