Review

Mammalian Genome

, Volume 17, Issue 3, pp 189-202

Open Access This content is freely available online to anyone, anywhere at any time.

Mammalian microRNAs: a small world for fine-tuning gene expression

  • Cinzia SevignaniAffiliated withDepartment of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College
  • , George A. CalinAffiliated withDepartment of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University
  • , Linda D. SiracusaAffiliated withDepartment of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College Email author 
  • , Carlo M. CroceAffiliated withDepartment of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University Email author 

Abstract

The basis of eukaryotic complexity is an intricate genetic architecture where parallel systems are involved in tuning gene expression, via RNA-DNA, RNA-RNA, RNA-protein, and DNA-protein interactions. In higher organisms, about 97% of the transcriptional output is represented by noncoding RNA (ncRNA) encompassing not only rRNA, tRNA, introns, 5′ and 3′ untranslated regions, transposable elements, and intergenic regions, but also a large, rapidly emerging family named microRNAs. MicroRNAs are short 20-22-nucleotide RNA molecules that have been shown to regulate the expression of other genes in a variety of eukaryotic systems. MicroRNAs are formed from larger transcripts that fold to produce hairpin structures and serve as substrates for the cytoplasmic Dicer, a member of the RNase III enzyme family. A recent analysis of the genomic location of human microRNA genes suggested that 50% of microRNA genes are located in cancer-associated genomic regions or in fragile sites. This review focuses on the possible implications of microRNAs in post-transcriptional gene regulation in mammalian diseases, with particular focus on cancer. We argue that developing mouse models for deleted and/or overexpressed microRNAs will be of invaluable interest to decipher the regulatory networks where microRNAs are involved.