May 3, 2019

Joana Silva

9.45-10.00 Joana Silva

‘The role of mRNA capping in ESCs and differentiation’

The mRNA cap consists of a series of co-transcriptional modifications on the nascent transcripts that confer protection from degradation and mediate RNA processing and translation. The addition of an inverted guanosine cap to the 5’-end of the mRNA and its subsequent methylation along with the first and second transcribed nucleotides are catalyzed by several enzymes that take place to form a complete cap structure. Recent studies have demonstrated how cell-housekeeping processes such as mRNA splicing and protein synthesis can have unexpected roles in fate determination. Our lab has previously shown the importance of the regulation of RAM, protein that takes part in the methylation of the cap structure, in the maintenance of pluripotency and neural differentiation. In this project, we aim to further characterize the expression of the capping enzymes in the early stages of mouse embryo development and are investigating the mechanisms by which mRNA capping determines the differentiation process. Our data indicates a role for CMTR1, enzyme responsible for 2-O-methylation of the first transcribed nucleotide, in controlling the first stages of exit from pluripotency as its absence increases the expression of pluripotency markers and impairs the process of proliferation in differentiation conditions.