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The molecular processes which control the development and function of lymphocytes have been extensively studied from the perspective of cell surface receptors and their associated intracellular signalling. Also, many transcription factors which repress or promote the production of mRNA have been identified as being essential for lymphocyte development and activation. These studies have revealed that genes, molecules and pathways that are used early in the development of lymphocytes are re-used in fully mature cells as part of the response to infection. Examples of this include signalling pathways such as the PI3K and ERK pathways and transcription factors such as the E2A, BCL-6, STATs, GATA-3 or Notch-1; all are required for lymphocyte development, but also for the proper responses of mature lymphocytes. This important principle has been revealed using mouse models in which genes are deleted at specific developmental stages.
Changes in gene transcription alone do not account for many dynamic changes in gene expression. However, the contribution of post-transcriptional regulation is still unclear. The discovery of microRNA-mediated control has led to an explosion of research into this fundamental mechanism regulating gene expression. However, there are approximately 700 RNA-binding proteins (RBP) encoded within the genome and, for most, their functions in splicing, polyadenylation, mRNA transport and localisation, as well as mRNA stability and translational efficiency remain to be defined. Furthermore, appreciation of the regulation of RBP function via phosphorylation, ubiquitination etc will be crucial for a complete understanding of signal transduction. (More...)
Babraham Institute - Babraham Research Campus - Cambridge - United Kingdom