Alternative titles; symbols
HGNC Approved Gene Symbol: EXOSC4
Cytogenetic location: 8q24.3 Genomic coordinates (GRCh38) : 8:144,064,056-144,080,648 (from NCBI)
Inherently unstable mammalian mRNAs contain AU-rich elements (AREs) within their 3-prime untranslated regions. In yeast, 3-prime-to-5-prime mRNA degradation is mediated by the exosome, a multisubunit particle. Chen et al. (2001) purified and characterized the human exosome by mass spectrometry and found its composition to be similar to its yeast counterpart. They identified the following protein subunits within the human exosome: p7, which is homologous to the yeast Rrp4 protein (602238); p8, which is homologous to the yeast Rrp42 protein (606488); p9, which is homologous to the yeast Rrp43 protein (OIP2; 606019); p10, which is homologous to the yeast Rrp40 protein (606489); p11, which is homologous to the yeast Mtr3 protein (606490); p12A, which is homologous to the yeast Rrp41 protein; p12B, which is homologous to the yeast Rrp46 protein (606492); and p13, which is homologous to the yeast Csl4 protein (606493). They also identified 2 exosome-associated factors, p1 (600478) and p14 (MPP6; 605500), that were not homologous to any yeast exosome components.
By searching an EST database for homologs of yeast exosome components, followed by PCR on a teratocarcinoma cell line and 5-prime RACE using placenta RNA, Brouwer et al. (2001) isolated cDNAs encoding RRP40, RRP41, and RRP46. The deduced 245-amino acid RRP41 protein is 96% and approximately 40% identical to the mouse and yeast sequences, respectively. Western blot analysis and immunofluorescence microscopy showed expression of a 27-kD protein in the nucleus, with a larger form expressed in the cytoplasm and the highest concentration in nucleolus.
Using a cell-free RNA decay system, Chen et al. (2001) demonstrated that the mammalian exosome is required for rapid degradation of ARE-containing RNAs but not for poly(A) shortening. They found that the mammalian exosome does not recognize ARE-containing RNAs on its own. ARE recognition required certain ARE-binding proteins that could interact with the exosome and recruit it to unstable RNAs, thereby promoting their rapid degradation.
Functional analysis by Brouwer et al. (2001) supported the conclusion that RRP41 is present in human exosomes in a complex displaying 3-prime-to-5-prime exonuclease activity.
Gross (2014) mapped the EXOSC4 gene to chromosome 8q24.3 based on an alignment of the EXOSC4 sequence (GenBank AF281133) with the genomic sequence (GRCh37).
Brouwer, R., Allmang, C., Raijmakers, R., van Aarssen, Y., Egberts, W. V., Petfalski, E., van Venrooij, W. J., Tollervey, D., Pruijn, G. J. M. Three novel components of the human exosome. J. Biol. Chem. 276: 6177-6184, 2001. [PubMed: 11110791] [Full Text: https://doi.org/10.1074/jbc.M007603200]
Chen, C.-Y., Gherzi, R., Ong, S.-E., Chan, E. L., Raijmakers, R., Pruijn, G. J. M., Stoecklin, G., Moroni, C., Mann, M., Karin, M. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107: 451-464, 2001. [PubMed: 11719186] [Full Text: https://doi.org/10.1016/s0092-8674(01)00578-5]
Gross, M. B. Personal Communication. Baltimore, Md. 6/25/2014.