Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones
Author:
Ali Mohammad A.M.,Garcia-Vilas Javier A.,Cromwell Christopher R.,Hubbard Basil P.,Hendzel Michael J.,Schulz Richard
Abstract
AbstractCell proliferation and survival require continuous ribosome biogenesis and protein synthesis. Genes encoding ribosomal RNA (rRNA) are physically located in a specialized substructure within the nucleus known as the nucleolus, which has a central role in the biogenesis of ribosomes. Matrix metalloproteinase-2 (MMP-2) was previously detected in the nucleus. However, its role there is elusive. Herein we report that MMP-2 resides within the nucleolus to regulate rRNA transcription. MMP-2 is enriched at the promoter region of rRNA gene repeats and its inhibition downregulates pre-rRNA transcription. The N-terminal tail of histone H3 is clipped by MMP-2 in the nucleolus and is associated with increased rRNA transcription. Knocking down/out MMP-2 or inhibiting its activity prevents histone H3 cleavage and reduces both rRNA transcription and cell proliferation. In addition to the known extracellular roles of MMP-2 in tumor growth, our data reveal an epigenetic mechanism whereby intranucleolar MMP-2 regulates cell proliferation through histone proteolysis and facilitation of rRNA transcription.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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