Dis3-like 1: a novel exoribonuclease associated with the human exosome

Abstract

The exosome is an exoribonuclease complex involved in the degradation and maturation of a wide variety of RNAs. The nine‐subunit core of the eukaryotic exosome is catalytically inactive and may have an architectural function and mediate substrate binding. In Saccharomyces cerevisiae, the associated Dis3 and Rrp6 provide the exoribonucleolytic activity. The human exosome‐associated Rrp6 counterpart contributes to its activity, whereas the human Dis3 protein is not detectably associated with the exosome. Here, a proteomic analysis of immunoaffinity‐purified human exosome complexes identified a novel exosome‐associated exoribonuclease, human Dis3‐like exonuclease 1 (hDis3L1), which was confirmed to associate with the exosome core by co‐immunoprecipitation. In contrast to the nuclear localization of Dis3, hDis3L1 exclusively localized to the cytoplasm. The hDis3L1 isolated from transfected cells degraded RNA in an exoribonucleolytic manner, and its RNB domain seemed to mediate this activity. The siRNA‐mediated knockdown of hDis3L1 in HeLa cells resulted in elevated levels of poly(A)‐tailed 28S rRNA degradation intermediates, indicating the involvement of hDis3L1 in cytoplasmic RNA decay. Taken together, these data indicate that hDis3L1 is a novel exosome‐associated exoribonuclease in the cytoplasm of human cells.

Different nuclease requirements for exosome-mediated degradation of normal and nonstop mRNAs

“…The catalytic activity is provided by a 10th essential subunit, Rrp44p (2,5,6). This protein is similar to RNase II in that it contains three putative RNA binding domains that flank an RNB domain (3,(7)(8)(9)(10).…”

Catalytic Properties of the Eukaryotic Exosome

“…[15][16] Interestingly, the single human Rrp6 protein is found not only in the nucleus (with nucleolar enrichment typical of exosome ring proteins) but also in the cytoplasm, unlike its yeast counterpart. [17][18] In plants on the other hand, while only one protein of the Dis3 family is encoded in currently known plant genomes, three genes of the RRP6 family are present in Arabidopsis, rice and poplar, encoding the proteins AtRRP6L1, AtRRP6L2 and AtRRP6L3 in Arabidopsis.…”

Twins take the job

“…Surprisingly, however, the human RRP6 factor (hRRP6, also designated PM/Scl-100) was reported to be present in both the nucleus and cytoplasm (Brouwer et al, 2001;van Dijk et al, 2007), whereas DIS3 was not found in exosome preparations (Chen et al, 2001). Tomecki et al (2010) and Staals et al (2010) now report that the genome from human beings and some other higher eukaryotes encodes three DIS3 paralogs: hDIS3, DIS3-like 1 (hDIS3L1) and DIS3-like 2 (hDIS3L2). Functional analysis indicates that these proteins have different functions as only hDIS3 complements a yeast DIS3 deletion.…”

“…Recent analysis of higher eukaryotic exosomes reveals some differences challenging this idea. In this issue of The EMBO Journal, Tomecki et al (2010) and Staals et al (2010) provide new insights into the composition and function of the human exosome, with implications for our understanding on the organization, function and localization of this complex in these cells.The exosome is responsible for many RNA processing and degradation reactions in the nucleus and cytoplasm (Lykke-Andersen et al, 2009). Yeast exosome is composed of a nine subunit ring structure to which Dis3 binds to form the exosome core.…”

“…Recent analysis of higher eukaryotic exosomes reveals some differences challenging this idea. In this issue of The EMBO Journal, Tomecki et al (2010) and Staals et al (2010) provide new insights into the composition and function of the human exosome, with implications for our understanding on the organization, function and localization of this complex in these cells.…”