Alternative titles; symbols
HGNC Approved Gene Symbol: TSEN34
Cytogenetic location: 19q13.42 Genomic coordinates (GRCh38): 19:54,189,441-54,194,532 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19q13.42 | ?Pontocerebellar hypoplasia type 2C | 612390 | Autosomal recessive | 3 |
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).
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.
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.
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).
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.
Budde, B. S., Namavar, Y., Barth, P. G., Poll-The, B. T., Nurnberg, G., Becker, C., van Ruissen, F., Weterman, M. A. J., Fluiter, K., te Beek, E. T., Aronica, E., van der Knaap, M. S., and 26 others. tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nature Genet. 40: 1113-1118, 2008. [PubMed: 18711368] [Full Text: https://doi.org/10.1038/ng.204]
Paushkin, S. V., Patel, M., Furia, B. S., Peltz, S. W., Trotta, C. R. Identification of a human endonuclease complex reveals a link between tRNA splicing and pre-mRNA 3-prime end formation. Cell 117: 311-321, 2004. [PubMed: 15109492] [Full Text: https://doi.org/10.1016/s0092-8674(04)00342-3]
Wende, H., Volz, A., Ziegler, A. Extensive gene duplications and a large inversion characterize the human leukocyte receptor cluster. Immunogenetics 51: 703-713, 2000. Note: Erratum: Immunogenetics 52: 308 only, 2001. [PubMed: 10941842] [Full Text: https://doi.org/10.1007/s002510000187]