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Title: Expression of different functional isoforms in haematopoiesis
Authors: Grech, Godfrey
Pollacco, Joël
Portelli, Mark
Sacco, Keith
Baldacchino, Shawn
Grixti, Justine
Saliba, Christian
Keywords: Hematopoiesis
Alternative splicing
Issue Date: 2014
Publisher: Springer
Citation: Grech, G., Pollacco, J., Portelli, M., Sacco, K., Baldacchino, S., Grixti, J, & Saliba, C. (2014). Expression of different functional isoforms in haematopoiesis.International Journal of Hematology, 99(1), 4-11.
Abstract: Haematopoiesis is a complex process regulated at various levels facilitating rapid responses to external factors including stress, modulation of lineage commitment and terminal differentiation of progenitors. Although the transcription program determines the RNA pool of a cell, various mRNA strands can be obtained from the same template, giving rise to multiple protein isoforms. The majority of variants and isoforms co-occur in normal haematopoietic cells or are differentially expressed at various maturity stages of progenitor maturation and cellular differentiation within the same lineage or across lineages. Genetic aberrations or specific cellular states result in the predominant expression of abnormal isoforms leading to deregulation and disease. The presence of upstream open reading frames (uORF) in 50 untranslated regions (UTRs) of a transcript, couples the utilization of start codons with the cellular status and availability of translation initiation factors (eIFs). In addition, tissue-specific and cell lineage-specific alternative promoter use, regulates several transcription factors producing transcript variants with variable 50 exons. In this review, we propose to give a detailed account of the differential isoform formation, causing haematological malignancies.
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