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MicroRNA Cotargeting Linked to Lupus

MicroRNAs with close or overlapping target sites are often highly conserved and can play a role in lupus and other diseases, according to a study in BMC Biology this week. MiRNAs are small, non-coding RNAs that bind to and repress specific mRNAs, and their dysfunction has been linked to a range of diseases. Multiple miRNAs can target closely spaced target sites to achieve stronger mRNA repression, but the pathological significance of such cotargeting is unknown. To investigate, a team led by Nagoya University researchers performed miRNA expression profiling in a mouse model of systemic lupus erythematosus and identified two miRNAs — miR-128 and miR-148a — that were downregulated in certain immune cells highly implicated in the disease. Further analysis revealed that the two miRNAs target a pro-inflammatory transcription factor via extensively overlapping target sites to suppress inflammatory responses. The study's authors also demonstrated that such overlap is prevalent among broadly conserved miRNAs and their target sites, and they uncovered two major conservation classes of target sites: those conserved among eutherian mammals and between humans and the bony fish Coelacanth. "These findings highlight the importance of perturbed miRNA cotargeting in human pathology and unique evolutionary aspects of miRNA cotargeting and miRNA target site conservation," they write.

The Scan

Harvard Team Report One-Time Base Editing Treatment for Motor Neuron Disease in Mice

A base-editing approach restored SMN levels and improved motor function in a mouse model of spinal muscular atrophy, a new Science paper reports.

International Team Examines History of North American Horses

Genetic and other analyses presented in Science find that horses spread to the northern Rockies and Great Plains by the first half of the 17th century.

New Study Examines Genetic Dominance Within UK Biobank

Researchers analyze instances of genetic dominance within UK Biobank data, as they report in Science.

Cell Signaling Pathway Identified as Metastasis Suppressor

A new study in Nature homes in on the STING pathway as a suppressor of metastasis in a mouse model of lung cancer.