The traditional central dogma of molecular biology is that protein-coding gene or DNA is transcribed into messenger RNA (mRNA), which is then translated into protein. Proteins then play their role in structure and function in the physiology of the human body. However, the completion of the Human Genome Project led to the surprising discovery that there are only about 20,000 protein coding genes in the human genome. These genes represent only about 2% of the entire genome. Surely the rest of the genome is not made up of junk DNA. Since the worm has roughly the same number of protein-coding genes as the human, the complexity of humans must be explained by the non-coding parts of the genome.
More than 90 percent of the human genome is likely transcribed into RNA that is not translated into protein. These are known as non-coding RNAs (ncRNAs). Long non-coding RNAs are transcribed RNA molecules larger than 200 nucleotides in length. Different long ncRNAs are expressed during different stages of development. Specific long ncRNAs are expressed in certain cells and localize to specific locations in the cell. Long ncRNAs play regulatory and functional roles in contributing to the complexity of the human physiology. Scientists are only just beginning to understand the numerous roles of long ncRNAs.
Regulatory functions of long ncRNAs
There is a number of ways in which long ncRNAs can regulate gene expression. They can directly affect the transcription of a protein-coding gene. Long ncRNAs can bind to mRNA transcripts and block translation. They recruit other RNAs known as silencing RNAs or siRNAs, which cause the degradation of mRNA transcripts.
Long ncRNAs can fold into complex structural forms that are specific for binding to proteins. The RNA-protein complexes can regulate the activity or localization of the protein.
Processing of long ncRNAs
Long ncRNAs can be processed into small RNAs such as microRNAs (miRNAs) and silencing RNAs (siRNAs). These small RNAs also have independent regulatory roles in gene expression.
Role of long ncRNAs in human disease
Alterations in long ncRNA expression have been observed in many cancers, suggesting that long ncRNAs may also play a role in cancer development. Other diseases known to involve long ncRNAs include alpha thalassemia, Alzheimer’s disease, and myotonic dystrophy. Future research into long ncRNA function may result in their use as biomarkers for detecting disease or as specific therapeutic targets.