A non-canonical role for HIF-1α: redirecting DGCR8 to the RNA exosome for snoRNA degradation and translational modulation.

ABSTRACT: The RNA exosome complex (EC) is a multi-protein complex responsible for RNA surveillance. Guided by specific adaptor factors, the EC recognizes RNA species as substrates for processing or degradation. Although its basic structure and components are documented, the regulatory mechanisms that enable this fundamental machinery to respond to biological signals remain unclear. Here, we demonstrate that hypoxia-inducible factor 1-alpha (HIF-1α) brings DGCR8 to associate with the EC in an RNA-independent manner and shifts DGCR8's RNA-binding preference toward small nucleolar RNAs (snoRNAs). This circuit triggers the snoRNA degradation without affecting their transcription or processing, ultimately impairing ribosomal RNA (rRNA) modifications such as pseudouridylation and 2'-O-methylation, comprom

SUBMITTER: Li JN 

PROVIDER: S-EPMC12862392 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature