Computation of Putative Targets for Human and Mouse snoRNAs, Responsible for Prader-Willi Syndrome

摘要

This Small nucleolar RNA (snoRNA) are a group of non-protein-coding RNA molecules among hundreds of others in the human genome. These molecules bind specifically to other cellular RNA targets via base pairing to form short, double-stranded structures. This binding causes the snoRNA targets to undergo specific chemical modifications. There are a number of (orphan) snoRNAs whose targets are still unknown; yet they clearly seem to play an important cellular function as their removal seems to cause genetic diseases like Prader-Willi Syndrome. In this project we aim to computationally predict targets for a specific group of orphan snoRNA of human and mouse (known as HBII-85 and MBII-85 respectively) that are known to be associated directly in the development of Prader-Willi Syndrome [1]. We started off by modifying our previously published snoTARGET program [2], to search for targets in the entire set of human and mouse genomic sequences. Then we generated a computational pipeline to characterize targets common to these two species. This resulted in the discovery of dozens of putative HBII-85/MBII-85 targets within the evolutionarily conserved segments of mRNAs, introns, and intergenic regions. Several of these targets have been found to be very well conserved evolutionarily among other mammals, and seem to have distinctive secondary structures detected by Evofold program [3]. Hence these targets can form the primary objects for further experimental validation. This could enhance the understanding of the function and clinical relevance of this group of snoRNA and could pave novel modes of intervention for arresting or alleviating the Prader-Willi Syndrome. The human genome contains hundreds of small non-protein-coding RNA molecules of which one group are the snoRNA (small nucleolar RNA). These molecules bind specifically to other cellular RNA targets via base pairing to form short, double-stranded structures. This binding causes the snoRNA targets to undergo specific che-mical modifications. There are a number of (orphan) snoRNAs whose targets are still unknown; yet, because their removal causes genetic diseases such as Prader-Willi Syndrome, they clearly seem to play an important cellular function. In this project we aimed to computationally predict targets for a specific group of orphan snoRNA of human and mouse (known as HBII-85 and MBII-85 respectively) that are known to be directly involved in the development of Prader-Willi Syndrome. To fulfill this task we modified our previously published snoTARGET program, to search for targets in the entire set of human and mouse genomic sequences. Then we generated a computational pipeline to characterize targets common for these two species. This approach resulted in the discovery of dozens of putative HBII-85/MBII-85 targets within the evolutionary conserved segments of mRNAs, introns, and intergenic regions. Several of these targets are located within mammalian-wide evolutionary conserved sequences that have distinctive secondary structures detected by Evofold program. These targets are the primary objects for further experimental validation of our findings.