Dr. David Bartel and colleagues describe a novel experimental system for genome-wide quantitative analysis of miRNA target expression in miRNA-expressing cells. They found that in the developing zebrafish embryo, miRNA targets are commonly expressed at lower levels in miRNA-expressing cells, suggesting that miRNAs work in concert with other regulatory processes to dampen target gene expression in specific miRNA-expressing cells.

Separately, Dr. Antonio Giraldez and clleagues detail their identification of the muscle-specific miRNA targets in the zebrafish embryo. They report that miR-1 and miR-133 are they key muscle regulatory miRNAs, and that they function by mediating actin organization in the developing muscle.

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Researchers also studied blood samples from healthy human volunteers to verify the impact of genetic differences in IFRD1 on neutrophil regulation. They found that the same IFRD1 variations that modified cystic fibrosis lung disease severity also altered neutrophil function in the healthy volunteers.

In a finding that may be the basis for novel approaches to treating cystic fibrosis, the investigators also determined that IFRD1's regulation of neutrophil function depends on its interaction with histone deacetylases “ enzymes important for regulating gene transcription. Additional research is needed to better understand this interaction before its potential role for treatment is known.

"It's possible that IFRD1 itself could become a target for treatment, but right now it's a signpost to pathways for further study," Dr. Karp said. "We want to find out what other genes and proteins IFRD1 interacts with, and how this is connected to inflammation in cystic fibrosis lung disease."

According to the National Cystic Fibrosis Foundation, cystic fibrosis is an inherited chronic disease that affects the lungs and digestive systems of about 30,000 children and adults in the United States and 70,000 worldwide. The defect in the CFTR gene causes the body to produce unusually thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. It also obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.

In the 1950s, few children with cystic fibrosis lived to attend elementary school. Today, advances in research and medical treatments have allowed people to live into their 30s or 40s. Despite these advances, the norm remains an ongoing decline in pulmonary function.

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