Small Nucleolar RNAs (snoRNAs) Can Regulate Alternative Splicing; May Explain Roles in Prader-Willi Syndrome & Some Cancers

An international team of researchers has discovered unexpected functions of small nucleolar RNAs (snoRNAs) that may explain the cause of some human diseases. The research, led by Professor Stefan Stamm from the University of Kentucky and Professor Ruth Sperling from the Hebrew University of Jerusalem, appears in the March 22, 2016 issue PNAS. The article is titled “Dual Function of C/D Box Small Nucleolar RNAs in rRNA Modification and Alternative Pre-mRNA Splicing.” The loss of snoRNAs is associated with a number of diseases, including Prader-Willi syndrome, which characterized by an insatiable appetite, and several forms of cancer: smoldering multiple myeloma, breast cancer, and prostate cancer. Also, genetic duplications of some snoRNAs could play a role in autism. However, it has not previously been clear how changes in snoRNA expression could lead to these diseases. Using RNA sequencing and molecular biology techniques, the researchers have now found that often snoRNAs not only modify ribosomes, but actually perform a dual function: they can also regulate alternative splicing, resulting in regulating the alternative inclusion of small pieces in proteins, which regulates protein function, thus inhibiting the generation of aberrant protein variants. These new functions can explain the role of snoRNAs in human diseases, as upon their loss the formation of aberrant protein variants may no longer be prevented. In mechanistic studies, the researchers also showed that short synthetic RNAs could be used as a substitute for the missing snoRNAs. This could point to a possible therapy for genetic hyperphagia (a condition that causes extreme hunger or appetite) and some forms of cancer. “This research helps us to understand the unexpected dual role of snoRNAs in gene regulation.
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