Alternative titles; symbols
HGNC Approved Gene Symbol: DIS3
Cytogenetic location: 13q21.33 Genomic coordinates (GRCh38) : 13:72,752,169-72,781,900 (from NCBI)
The RNA exosome is an approximately 400-kD multimeric ribonucleolytic complex that participates in both endonucleolytic and 3-prime/5-prime exonucleolytic activity in RNA processing and in the degradation of a variety of RNA substrates. DIS3 is a catalytic subunit that has both endonucleolytic and 3-prime/5-prime exonucleolytic activity (summary by Tomecki et al., 2010).
By randomly sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1999) cloned DIS3, which they designated KIAA1008. The deduced 928-amino acid protein shares 44.5% identity with the mitotic control protein Dis3 of S. pombe. PCR-ELISA detected low to moderate expression in all tissues and brain regions tested, with highest expression in testis and moderate expression in kidney, ovary, corpus callosum, spinal cord, and fetal brain.
By sequence analysis of chromosome 13q21-q22 to identify a breast cancer susceptibility gene, Rozenblum et al. (2002) identified DIS3. The deduced protein contains 958 amino acids. Northern blot analysis detected ubiquitous expression.
By searching a human EST database for sequences similar to yeast Dis3, Tomecki et al. (2010) identified DIS3. The deduced 958-amino acid protein contains a well conserved N-terminal PIN domain, followed by 2 cold-shock domains, an RNB exonuclease catalytic domain, and a C-terminal S1 domain. DIS3 localized predominantly to the nucleus in HEK293 and HeLa cells, with exclusion from nucleoli.
Tomecki et al. (2010) found that epitope-tagged human DIS3 or DIS3L (614183) coimmunoprecipitated with core exosome subunits from transfected HEK293 cells. Depletion of DIS3 or RRP6 (EXOSC10; 605960) from HeLa cells resulted in the accumulation of nuclear 5.8 rRNA precursors, an effect that was exacerbated by RRP6/DIS3 double knockdown. Double depletion also resulted in partial stabilization of cytoplasmic MYC (190080) mRNA. DIS3 purified from transfected HEK293 cells showed 3-prime/5-prime exonuclease activity against single-stranded RNA and endonuclease activity against a circular RNA substrate. Domain analysis revealed that the PIN and RNB domains of DIS3 conferred endonuclease and exonuclease activity, respectively. Expression of human DIS3 could partially complement Dis3 depletion in yeast.
Rozenblum et al. (2002) determined that the DIS3 gene contains 21 exons and spans 26.5 kb.
By genomic sequence analysis, Rozenblum et al. (2002) mapped the DIS3 gene to chromosome 13q21-q22.
Gross (2014) mapped the DIS3 gene to chromosome 13q22.1 based on an alignment of the DIS3 sequence (GenBank AB001743) with the genomic sequence (GRCh37).
Gross, M. B. Personal Communication. Baltimore, Md. 6/25/2014.
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6: 63-70, 1999. [PubMed: 10231032] [Full Text: https://doi.org/10.1093/dnares/6.1.63]
Rozenblum, E., Vahteristo, P., Sandberg, T., Bergthorsson, J. T., Syrjakoski, K., Weaver, D., Haraldsson, K., Johannsdottir, H. K., Vehmanen, P., Nigam, S., Golberger, N., Robbins, C., and 12 others. A genomic map of a 6-Mb region at 13q21-q22 implicated in cancer development: identification and characterization of candidate genes. Hum. Genet. 110: 111-121, 2002. [PubMed: 11935316] [Full Text: https://doi.org/10.1007/s00439-001-0646-6]
Tomecki, R., Kristiansen, M. S., Lykke-Andersen, S., Chlebowski, A., Larsen, K. M., Szczesny, R. J., Drazkowska, K., Pastula, A., Andersen, J. S., Stepien, P. P., Dziembowski, A., Jensen, T. H. The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L. EMBO J. 29: 2342-2357, 2010. [PubMed: 20531386] [Full Text: https://doi.org/10.1038/emboj.2010.121]