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Biological role of microRNAs in the DLK1 GTL2 imprinted domain.

Final Report Summary - CALLIMIR (Biological role of microRNAs in the DLK1 GTL2 imprinted domain)

The aim of the CALLIMIR project was to make a significant contribution to understanding the biological role of non-coding RNA genes in the mammalian genome, including miRNAs. It is increasingly recognised that in addition to protein-encoding mRNA, genome transcription generates a flurry of so-called non-coding RNA genes. These include well-known ribosomal RNAs, transfer RNAs, as well as small nuclear and nucleolar RNAs. However, the family of non-coding RNA genes has recently witnessed a spectacular expansion with the discovery of:
(i) a multitude of small RNA species involved in RNAi-related biology (including miRNAs); and
(ii) myriads of long, non-coding RNA species of essentially unknown function. Deciphering the roles of these non-coding RNA genes has emerged as one of the hottest topics in molecular biology today.

The CALLIMIR project has published work on the phenotypic and epigenetic consequences of the IG-DMR deletion supporting the role of maternally expressed non-coding RNAs in the domain. Using multicolour RNA FISH at the single nucleus level, the consortium has demonstrated that non-coding RNAs transcribed from the Dlk1-Gtl2 domain form large elongated nuclear track structures and accumulate as single-molecule nuclear RNA foci within the interchromatin space.

By studying a muscular hypertrophy in sheep, the consortium has identified an important novel class of mutations that affect the interaction between miRNAs and their targets. Bioinformatic analyses of SNPs databases for human and mice has demonstrated that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation. A publicly accessible database (Patrocles) that compiles this information has been posted on the World wide web (WWW).