Contribution of microRNAs to CLL Biology and Their Potential as New Biomarkers

After the complete description of the human genome (approximately 3x109 bases) the best estimates of protein-coding genes account for about 30,000 to 40,000 genes representing approximately 1% of the genome. A significantly remainder fraction of the genome is transcribed into RNAs that do not code for proteins which are classified as non-coding RNAs (ncRNAs) (Wright et al., 2001). These ncRNAs were unnoticed in the genome until recent improvements in high-throughput technology for gene expression assays led to the discovery that most human transcriptional units are ncRNAs. These ncRNAs have been segregated into two main classes; long and small non-coding RNAs. Over the last almost two decades, the family of small ncRNAs (i.e. microRNAs, siRNAs and piRNAs) has grown in number and relevance and emerged as new key regulators of gene expression. These small ncRNAs, which are ~19–32 nucleotides (nt) in length, act as sequence-specific triggers for mRNA degradation, translation repression, heterochromatin formation and genome stability affecting biological functions either by posttranscriptional silencing or stimulating transcript degradation. The most well known small ncRNAs are the microRNAs (miRNAs). To date, more than 1500 human miRNAs genes have been annotated. They are organized as monoor policystronic transcriptional units in the genome located either in intergenic regions or within introns and exons of non-coding as well as coding transcription units (miRBase, release 18: November 2011).