The era of genome and transcriptome sequencing revealed that the vast majority of the DNA is transcribed into RNA, although proteins are only encoded by about 2% of the DNA. Within the pool of non protein-coding RNAs (ncRNAs) some have long been known to function in protein translation or mRNA processing (tRNAs, rRNAs or snRNAs) and several more functional RNA classes have been described within the last decade that are involved in basic biological processes like genome surveillance (e.g. piRNA), chromosome structure (e.g. Xist) and the regulation of gene expression (e.g. miRNAs). It remains controversial what proportion of the ncRNAs are of functional relevance and what amount is useless, so called transcriptional “noise”.
Of the more recently discovered short ncRNAs, miRNAs are among the best studied. MiRNAs are short ncRNAs (20-26nt) that regulate expression of approximately 60% of the protein-coding genes by mediating mRNA degradation or inhibiting their translation. In cancer, genetic or epigenetic alterations in miRNAs or their processing machinery are common. As miRNAs can regulate more than half of the proteome, and therefore affect complex regulatory circuits, their deregulation has a widespread impact in cancer and miRNAs have been implicated in every single aspect of tumor biology. MiRNAs may either enhance the expression of oncogenes or decrease the abundance of tumor suppressors. MiRNAs are also responsive to microenvironmental changes and thus, mediate the crosstalk between the tumor and its environment and affect for example angiogenesis or immune evasion. Several miRNA families have been implicated in metastasis, and exosome-packed miRNAs may contribute to organ-specific metastasis.
Another group of ncRNAs that received much attention over the last few years are long ncRNAs. Only a few of the heterogeneous group of lncRNAs are known to be of functional relevance in biological processes as epigenetic control, transcriptional and post-transcriptional regulation. As lncRNAs are expressed in a lineage-dependent manner and often deregulated in caner, they gained much attention in the field of cancer research and oncogenic or tumor-suppressor activity has been assigned to some lncRNAs.
Did you know that at least 80% of the human genome is transcribed into RNA, while – so far – a functional role has only been revealed for a small subset of these?