Inactivation of the exosome ribonuclease DIS3 triggers the pluripotency factor LIN28B, repressing let-7 miRNAs and unleashing MYC and RAS.

ABSTRACT: Somatic mutations affecting DIS3, the catalytic component of the RNA exosome, have been found in up to 18% of patients affected by the hematological cancer multiple myeloma. Here we show that DIS3 targets and degrades the pluripotency factor LIN28B. In cancer cells, DIS3 inactivation leads to enhanced LIN28B expression, thus disrupting the let-7 miRNAs tumor suppressor network and ultimately increasing protein levels of crucial oncogenes such as MYC and RAS. DIS3 represents the catalytic component of the exosome. The exosome is required for cell viability and targets several RNA species, including pre-mRNAs, pre-tRNAs, pre-rRNAs, snRNAs and snoRNAs. To gain insight on the macular wiring underlying DIS3 activity in mammalian cells, we comprehensively evaluated expression profiles, including

ORGANISM(S): Homo sapiens

SUBMITTER: Antonino Neri 

PROVIDER: E-GEOD-55246 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress