The transcriptional output of mammalian genomes is much more complex than previously through as illustrated by the recent identification of a huge number of transcripts lacking protein-coding potential (also referred to as noncoding RNAs, ncRNAs or small regulatory RNAs). Although functional validity is still lacking for the vast majority of them, ncRNAs are now believed to be key players in many aspects of gene expression.
Our research interest focused on hundreds microRNA and C/D snoRNAs whose genes are clustered at three distinct chromosomal loci positioned at human 14q32/mouse distal 12 (the so-called Dlk1-Dio3 domain), at human 15q11q13/mouse chr.7 (the so-called Snurf-Snrpn domain, also referred to as the Prader-Willi syndrome locus) and at human 19q13 (C19MC, the largest human microRNA gene cluster discovered so far).
These small ncRNA genes are expressed in a tissue-specific manner with strongest expression in the placenta and in the adult brain. More importantly, they are regulated by genomic imprinting, an epigenetic mechanism that leads to mono-allelic expression in a parent-of-origin specific manner, e.g. for a given gene, the paternal allele is turned on while the maternal allele is turned off.
Our ongoing research aims to elucidate the biogenesis and the physiological roles of these imprinted small RNA genes through the use of cell imaging approaches and knock-out mouse models.