SmD3 regulates intronic noncoding RNA biogenesis

Benjamin S. Scruggs, Carlos I. Michel, Daniel S. Ory, Jean E. Schaffer

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Accumulation of excess lipid in nonadipose tissues is associated with oxidative stress and organ dysfunction and plays an important role in diabetic complications. To elucidate molecular events critical for lipotoxicity, we used retroviral promoter trap mutagenesis to generate mutant Chinese hamster ovary cell lines resistant to lipotoxic and oxidative stress. A previous report of a mutant from this screen demonstrated that under lipotoxic conditions, small nucleolar RNAs (snoRNAs) in the rpL13a gene accumulate in the cytosol and serve as critical mediators of lipotoxic cell death. We now report a novel, independent mutant in which a single provirus disrupted one allele of the gene encoding the spliceosomal protein SmD3, creating a model of haploinsufficiency. We show that snoRNA expression and the abundance of snoRNA-containing intron lariats are decreased in SmD3 mutant cells, even though haploinsufficiency of SmD3 supports pre-mRNA splicing. The mechanism through which SmD3 regulates the expression of intronic snoRNAs likely involves effects of SmD3 on the levels of small nuclear RNAs (snRNAs) U4 and U5. Our data implicate SmD3 as a critical determinant in the processing of intronic noncoding RNAs in general and as an upstream mediator of metabolic stress response pathways through the regulation of snoRNA expression.

Original languageEnglish
Pages (from-to)4092-4103
Number of pages12
JournalMolecular and cellular biology
Volume32
Issue number20
DOIs
StatePublished - Oct 1 2012

Fingerprint Dive into the research topics of 'SmD3 regulates intronic noncoding RNA biogenesis'. Together they form a unique fingerprint.

  • Cite this