Representative microRNAs are differentially expressed in a 6-year-old (left), an 11-year-old (center) and a 13-year-old, all with autism and compared with age-matched controls. Up-regulated miRNAs are in red and down-regulated ones in green.

Some small fragments of RNA are expressed differently in people with autism than in controls, according to two new studies. The findings unveil another layer of complexity in the genetics of autism.

These pieces of single-stranded RNA — dubbed microRNAs or miRNAs — have wide-ranging, subtle effects on the production of many different proteins without affecting a cell’s underlying DNA code.

That may account for some of the widespread variation among people with autism, and even among family members who share genes, experts say.

“It’s possible that microRNAs can have some kind of regulatory role over multiple targets and affect them a little bit differently in different people,” says Kenneth Kosik, co-director of the Neuroscience Research Institute at the University of California, Santa Barbara.

Since their discovery in 1993, miRNAs have been thought to play a significant role in brain development and neuronal signaling. Researchers have found altered miRNA expression in many neurological diseases, including autism-related disorders such as fragile X syndrome, Rett syndrome and schizophrenia.

In July, Kosik and colleagues found, for the first time, that some miRNAs are also expressed differently in people with autism. Studying postmortem brain tissue samples of 13 people with autism and 13 controls, the team found that out of the 466 miRNAs analyzed, 9 are either up- or down-regulated in people with autism compared with controls.

In September, another team found that of 470 miRNAs analyzed, 9 are differentially expressed in people with autism, including 4 identified in the July report. For their study, Zohreh Talebizadeh and colleagues from the University of Missouri-Kansas City looked at miRNA expression in cultured blood cell lines from six people with autism and six controls.

In both studies, a computer algorithm predicted that a few of the differentially expressed miRNAs would target known autism-susceptibility genes. The July study’s list includes neurexin-1 (NRXN1) and SHANK3, and the August study points to neuroligin-3, PTEN, and two neurexin genes, NRXN1 and NRXN3.

If studies with larger sample sizes confirm these results, the next step is to confirm the target genes for the miRNAs. “For most miRNAs, the targets have not been confirmed yet,” says Talebizadeh. “We have a big task ahead of us.”

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