Spleen Transcriptome and Pathology in Tristetraprolin Deficiency
Members of the tristetraprolin (TTP) family of tandem zinc finger proteins influence mRNA levels by binding to AU-rich elements in the 3′ untranslated regions of specific mRNAs and promoting their deadenylation and decay. Patial et al. (p. 1395–1411) identified many changes in steady-state transcript levels in TTP-deficient mice that also lacked tumor necrosis factor receptors to prevent the inflammatory phenotype that normally accompanies TTP deficiency. Although a large proportion of the splenic transcriptome was affected by the absence of TTP, only a small fraction exhibited mRNA/pre-mRNA ratios that suggested increased posttranscriptional mRNA stability.
Tumor Necrosis Factor Alpha Upregulates Splicing Independently of Transcription and in Cooperation with Spt5
Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine known to induce transcription of many genes, primarily through activation of NF-κB. This induction relies in part on Spt5, the major subunit of the transcription elongation factor DSIF. Diamant et al. (p. 1342–1353) now show that TNF-α stimulation also enhances splicing in an unexpectedly large number of genes without inducing transcription. Accordingly, this enhancement is independent of NF-κB activation. The splicing effect is mediated by Spt5, and affected genes become enriched with the Spt5-RNA polymerase II (Pol II) complex following TNF-α treatment. This study identifies a novel activity of TNF-α and uncovers Pol II-Spt5 as a competent coordinator of cotranscriptional splicing.
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