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ABSTRACTThe exosome functions to regulate the cellular transcriptome through RNA biogenesis, surveillance, and decay. Mutations in Dis3, a catalytic subunit of the RNA exosome with separable endonuclease and exonuclease activities, are linked to multiple myeloma. Here we report that a cancer-associated DIS3allele, dis3E729K, provides evidence for DIS3functioning in mitotic fidelity in yeast. This dis3E729Kallele does not induce defects in 7S→5.8S rRNA processing, although it elicits a requirement for P-body function. While it does not significantly influence cell cycle progression alone, the allele reduces the efficiency of cell cycle arrest in strains with defects in kinetochore assembly. Finally, point mutations in the exonuclease domains of yeast Dis3 elicit genome instability phenotypes; however, these DIS3mutations do not increase DNA damage or RNA processing defects that lead to the accumulation of polyadenylated RNA in the nucleus. These data suggest that specific DIS3activities support mitotic fidelity in yeast.

Autonomic pathways are important in the regulation of both lower urinary tract and sexual function, and their interruption in neurological pathologies predictably results in variable urogenital dysfunction, depending mainly on the level of the lesion. A normal neurological examination of a patient with urogenital complaints should exclude an underlying neurological pathology, and the neurologist should become involved in the management of symptoms. Electromyography can be of value in the diagnosis and management of cauda equina lesions and multiple system atrophy, but neurophysiological investigations are of no importance in the diagnosis of neurogenic sexual dysfunction. Urodynamic studies have proven helpful in determining the type and management of lower urinary tract dysfunction. Oral anticholinergics usually combined with clean intermittent catheterizations are the first-line treatment options for neurogenic lower urinary tract dysfunction, with intravesical treatments emerging as the main alternative in intractable incontinence. The availability of effective oral phosphodiesterase inhibitors has revolutionized the management of erectile dysfunction, but treatment of ejaculatory and orgasmic disorders as well as of female sexual dysfunction still remains problematic.