Research Projects

The study confirms nuclear retention of utrophin-A mRNA in mouse myoblast C2C12, macrophage RAW264.7, and melanoma B16F10 cells. This finding has implications for designing therapeutic strategies for Duchenne Muscular Dystrophy (DMD), the most frequent genetic disorder worldwide. Utrophin can compensate for dystrophin deficiency, making it a potential therapeutic strategy. However, understanding the underlying mechanism of poly C binding protein 2 (PCBP2) mediated nuclear retention is crucial to develop a strategy to make utrophin-A more available for translation. The proposed project aims to characterize PCBP2 mediated nucleus-retained transcripts, decipher position effects of PCBP2 binding sites, and address whether RNA pol III transcripts and circular RNA can be retained in the nucleus in a PCBP2 dependent manner. Additionally, the study will check if PCBP2-retained mRNAs are localized into paraspeckles, the phase separated nuclear bodies sequestering many proteins and lncRNAs. Currently, only utrophin-A and follistatin are identified as mRNA targets of PCBP2 mediated nuclear retention. To identify other targets and understand the global impact of this novel function of PCBP2, RNA-seq analysis will be performed with cytosolic and nuclear fractions of PCBP2 overexpressed, silenced, and corresponding control C2C12 cells. Many proteins required for mRNA export are post-translationally modified, and the modification of PCBP2 is essential for their functions. Understanding different aspects of PCBP2 mediated nuclear retention of transcripts could have implications for designing therapeutic strategies for utrophin upregulation in DMD.