Research Projects

The 7-Methylguanosine (m7G) cap at the 5'-ends of eukaryotic transcripts is crucial for each step of RNA metabolism, including export to the cytoplasm, protein synthesis, and turn over. The addition of the m7G cap occurs after the synthesis of nascent transcript in the nucleus by mRNA Capping Enzyme (CE). Recent studies have shown that stable uncapped transcripts can be'recapped' in the cytoplasm by a cytoplasmic capping complex composed of CE (cCE), Nck1, 5'-monophosphate RNA kinase, and RNA methyl transferase (RNMT) in mammalian cells. The nuclear import mechanism of CE is not fully understood, but this proposal aims to identify putative nuclear localization signals of CE and validate them using in silico approaches. LncRNAs, which show similar architecture with mRNAs, have been identified as substrates of cCE and are stable in their uncapped forms. Cap Analysis of Gene Expression (CAGE) data has been established to find the correlation between uncapped ends and plausible recapping sites. However, a direct method should be established to identify the recapping sites. Recent studies have shown that cytoplasmic capping may regulate post transcriptional control of substrate lncRNAs either by enhancing their stability or generating novel peptides from these lncRNAs, which in turn mediate cellular recovery. This proposal will investigate the molecular mechanism of nuclear import of CE and the role of recapped lncRNAs in stress response, ultimately revealing the nuclear import pathway and their function in human health and diseases.