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Marina Falaleeva

There is remarkable number of functional non-coding RNAs in the human transcriptome which provide delicate tuning of cell metabolism. SnoRNAs are small noncoding RNAs that can be detected in the nucleolus. They reside within intronic sequences from which they are released through nuclease action during the processing of the pre-mRNA. In the cell C/D box snoRNAs are the part of RNA:protein complexes that participate in several processes. The most well understood function of snoRNP is 2’-O-methylation in ribosomal, transfer and small nuclear RNAs. This activity is achieved through the formation of a specific RNA:RNA duplex between the snoRNA and the target; where specific RNA modification is provided by the enzyme associated with snoRNA. Previously, in the Stamm’s lab another function of C/D box snoRNAs was uncovered. It has been established that one snoRNA - HBII-52 is a crucial part of pre-mRNA alternative splicing of serotonin receptor 2C (HTR2C). Furthermore, it was established by using MBII-52 snoRNA, a mouse ortholog of HBII-52, that snoRNA can be processed into shorter metabolically stable products termed psnoRNA (for processed snoRNAs). The psnoRNA likely recognizes target RNAs by sequence complementarity and influence splice-site selection by interfering with splicing regulatory proteins acting on pre-mRNA. The main focus of my project is to study MBII-52 and MBII-85 psnoRNA formation. Using gene knockdown cell lines and RNA protection assay I’m trying to uncover what cellular component(s) are responsible for formation of psnoRNA. In addition I’m trying to establish in vitro system of sno/psnoRNA processing, which will allow for experimental observation of the effect of different cellular components on RNA processing. Another goal of my project is to understand the relevance of psnoRNA within the cell. Using microarray technology, new targets of MBII-52 snoRNA were found; I will perform verification of this data using RT-PCR. That can help to delineate modes of action of this snoRNA which could be a member of new class of regulatory RNAs.


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