Computational analysis and in vivo validation of a microRNA encoded by the IBTK gene, a regulator of B-lymphocytes differentiation and survival.
MicroRNAs (miRNAs) are small single-stranded RNA molecules that play an essential role in the regulation of gene expression and cell physiology. Gene rearrangements occurring in the miRNA sequence are associated with cancer. The IBTK genetic locus is located in the genomic sequence 6q14.1 that undergoes chromosomal aberration in lymphoproliferative disorders. The IBTK gene encodes the proteins IBtk-alpha, beta and gamma that regulate the B cell receptor signalling through Bruton's tyrosine kinase, which promotes B cell survival and differentiation. Pro-MirII-based analysis predicted four precursors of microRNAs (pre-miR) encoded by introns 17, 21, 26 and the 3' un-translated region of the IBTK gene. Pre-miR-IBTK3, which was encoded by intron 26, was the effective substrate of RNase III Dicer in vitro as well as the precursor of an IBtk miRNA generated in vivo. By CLUSTALW-based analysis, pre-miR-IBTK3 homologues were found in Pan troglodytes, Pongo pygmaeus and Macaca mulatta, suggesting an evolutionary conserved function in primates.
Fiume
Giuseppe
G
Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Catanzaro, Italy. fiume@unicz.it
Rossi
Annalisa
A
Di Salle
Emanuela
E
Spatuzza
Carmen
C
Mallardo
Massimo
M
Scala
Giuseppe
G
Quinto
Ileana
I
D048868:Adaptor Proteins, Signal Transducing; D001402:B-Lymphocytes / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D015321:Gene Rearrangement; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C437966:IBtk protein, human; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs