SUMMARY PARAGRAPH for CSL4
The exosome complex possesses 3'-5' exonuclease and endoribonucleolytic activities that are essential for diverse ribonucleolytic processes in both the nucleus and the cytoplasm (8, 9, 10). The nuclear exosome is associated with the TRAMP complex and is involved in RNA catabolic processes including RNA surveillance (11, 12 and references therein), pre-mRNA turnover (13) and the production of mature 3' ends for snoRNAs, snRNAs and rRNAs (9, 14 and references therein). The cytoplasmic exosome is associated with Ski7p and the SKI complex and is involved in RNA catabolic processes that include both the routine turnover of normal mRNA (15) as well as the degradation of aberrant mRNAs (16 and references therein). The 10-subunit core exosome complex (Csl4p, Rrp4p, Rrp40p, Ski6p, Rrp42p, Rrp43p, Rrp45p, Rrp46p, Mtr3p, Dis3p) is the same in both locations, but the nuclear exosome contains an additional subunit (Rrp6p) and two additional accessory factors (Lrp1p, Mpp6p) (10).
Although the exosome was originally described as a "complex of exonucleases," with multiple subunits proposed to have RNase activity (8), later work has shown that this mechanism is unlikely in yeast. With the exception of Ski6p, none of the yeast subunits that show homology to E. coli RNase PH retain the active site residues seen in the bacterial or archael enzymes. Further research has also demonstrated that most, if not all, detectable enzymatic activity resides in the Dis3p and Rrp6p subunits (6, 7).
CSL4 encodes a core subunit of the exosome and is predicted to contain an S1 RNA binding domain (4, 5 and references therein). Like most exosome components, Csl4p is highly conserved among eukaryotes, including humans (hCsl4p (EXOSC1)) (6 and references therein). CSL4 is an essential gene (1, 17), but cells depleted for Csl4p accumulate aberrant forms of rRNA (4, 14). The csl4 mutation was originally isolated in a screen for mutations that were synthetically lethal with null mutations in the chromatin remodeling factor Cbf1p (1). Another mutant allele, ski4-1, was independantly isolated in a screen for mutations that caused the superkiller phenotype, which includes an increase in the concentration of viral dsRNAs (2); this mutant was later shown to also have defects in 3' to 5' mRNA degradation (3).
Last updated: 2009-09-09