MicroRNAs in B cell development and malignancy

In a relatively short time period, gene expression regulation by microRNAs (miRNAs) has changed the way that we view developmental and pathological processes. From initial discoveries in C. elegans, the identification of the novel small RNA biogenesis pathway and the identification of RNA interference, the field has moved rapidly [1-6]. The involvement of miRNAs in hematopoiesis has now been documented by numerous groups and they seem to regulate almost every aspect of hematopoietic development. In this review we focus on B cell development, where the importance of gene expression regulation has been appreciated for many years. miRNAs have emerged as critical regulators of gene expression and regulate many aspects of B cell development, and are dysregulated in B cell malignancies. Here, we review many of the studies that have been performed to delineate the roles of miRNAs in development and malignant transformation of B cells.miRNAs are non-protein coding RNAs of about 19-23 nucleotides. They are post-transcriptional gene regulators that bind to partially complementary sequences in the 3' UTR on target messenger RNA transcripts, thereby causing downregulation of the target [7]. They were first discovered in 1993 in C. elegans by Victor Ambros, during a study of lin-14. They identified a small RNA product encoded by lin-4 gene that is responsible for the downregulation of LIN-14 protein [2,3,8]. This central dogma of miRNA action has proven to stand the test of time, as miRNAs in most organisms are thought to behave similarly.miRNAs can be grouped in to at least three categories depending on their genomic location: exonic miRNAs in non-coding genes, intronic miRNAs in non-coding genes and intronic miRNAs in protein-coding genes [9]. miRNAs are expressed as long primary RNA (pri-miRNA) as part of RNA polymerase II-driven transcript [10]. Therefore, it is possible that some miRNAs are co-regulated with their host gene as a part of transcriptional regulation during B c