Gene stopper spotted
doi:10.1038/nindia.2009.103 Published online 15 April 2009
Geneticists have identified a new mechanism that stops the synthesis of the Interleukin-10 (IL-10) gene, a key orchestrator of the immune system1. This could provide new insights into managing various immunological diseases such as cancer, rheumatoid arthritis, asthma and infectious disorders.
IL-10 plays an important role in immune-regulatory events. Its dysregulation means one could suffer from any of these immunological diseases.
Using a combination of bioinformatics and molecular approaches, they found that microRNA (hsa-miR-106a) regulates IL-10 expression. They identified a novel microRNA mediated regulatory mechanism for IL-10, in which expression of hsa-miR-106a inhibits the synthesis of IL-10 through post-transcriptional regulation. A cluster of six microRNAs including hsa-miR-106a, present on chromosome X, is over expressed in 46% of human T-cell leukemias.
"We found that the transcription factors Sp1 and Egr1 regulate expression of hsa-miR-106a, demonstrating that transcriptional factors can exert both transcriptional and post-transcriptional control over key genes," says lead author Balaram Ghosh. MicroRNA mediated regulatory mechanisms for IL10 may be critical in maintaining immune homeostasis, he says.
Recently it was shown that the inhibitory function of natural killer cells in experimental model of visceral leishmaniasis, was correlated with high IL-10 production due to increased stability of IL-10 mRNA.
The team's work suggests a possible physiological role of hsa-miR-106a in regulating IL-10 levels. "We speculate that hsa-miR-106a is involved in fine-tuning IL-10 expression, thereby influencing the outcome of immune response to specific external stimuli," Ghosh adds.
Further studies examining the relevance of this regulatory mechanism to human health and disease are warranted especially in diseases like rheumatoid arthritis, asthma, cancer and viral infections where an altered IL-10 expression is an important aspect of disease pathogenesis.
- Sharma, A. et al. Posttranscriptional Regulation of Interleukin-10 Expression by has-miR-106a microRNA. Proc. Natl. Acad. Sci. USA 106, 5761-5766 (2009)