The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L.
The eukaryotic RNA exosome is a ribonucleolytic complex involved in RNA processing and turnover. It consists of a nine-subunit catalytically inert core that serves a structural function and participates in substrate recognition. Best defined in Saccharomyces cerevisiae, enzymatic activity comes from the associated subunits Dis3p (Rrp44p) and Rrp6p. The former is a nuclear and cytoplasmic RNase II/R-like enzyme, which possesses both processive exo- and endonuclease activities, whereas the latter is a distributive RNase D-like nuclear exonuclease. Although the exosome core is highly conserved, identity and arrangements of its catalytic subunits in different vertebrates remain elusive. Here, we demonstrate the association of two different Dis3p homologs--hDIS3 and hDIS3L--with the human exosome core. Interestingly, these factors display markedly different intracellular localizations: hDIS3 is mainly nuclear, whereas hDIS3L is strictly cytoplasmic. This compartmental distribution reflects the substrate preferences of the complex in vivo. Both hDIS3 and hDIS3L are active exonucleases; however, only hDIS3 has retained endonucleolytic activity. Our data suggest that three different ribonucleases can serve as catalytic subunits for the exosome in human cells.
Department of Biophysics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Rafal
R
Tomecki
Maiken S
MS
Kristiansen
Søren
S
Lykke-Andersen
Aleksander
A
Chlebowski
Katja M
KM
Larsen
Roman J
RJ
Szczesny
Karolina
K
Drazkowska
Agnieszka
A
Pastula
Jens S
JS
Andersen
Piotr P
PP
Stepien
Andrzej
A
Dziembowski
Torben Heick
TH
Jensen
D000595:Amino Acid Sequence; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism*; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D007527:Isoenzymes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C551544:DIS3L protein, human; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; D012260:Ribonucleases; C542283:DIS3 protein, S cerevisiae; C551543:DIS3 protein, human; C112610:RRP6 protein, S cerevisiae