RNA is key to the dark matter of the genome − scientists are sequencing it to illuminate human health and disease

Whispers of Nourishment: Unveiling the Role of Non-Coding RNA in ...

Although there are striking differences between the cells that make up your eyes, kidneys, brain and toes, the DNA blueprint for these cells is essentially the same. Where do those differences come from?

Scientists are realizing the defining qualities that make up each cell actually lie in a cousin of DNA called RNA.

RNA was long considered DNA’s boring biochemical relative. Researchers thought it merely takes the genetic information stored in DNA and delivers it to other parts of the cell, where it is then used to make the proteins that carry out the cell’s functions.

But only roughly 2% of DNA codes for protein. The rest – sequences of the DNA that don’t code for proteins – is what scientists consider the dark matter of the genome, and there is much interest in figuring out what it does. Therein lies much of the mystery and magic of RNA.

In this dark matter, noncoding DNA is transcribed into noncoding RNA. These include RNAs small and long that are never translated into protein, and have the potential to regulate the genome and generate the diversity of cells by turning on or off various genes. When these multifaceted RNAs go awry, they can lead to a broad array of diseases in people.

RNA scientists like those on our team are now working to sequence every human RNA as part of the Human RNome Project – the RNA equivalent of the Human Genome Project – to aid in human health and improve treatments for disease.

Diagram of DNA trascribed to RNA translated to protein

The central dogma of biology states that genetic information flows from DNA to RNA to protein.
National Human Genome Research Institute

RNA modifications orchestrate cell fate

DNA details how genes can become proteins, while RNA signals when and where these proteins are made. In other words, DNA is information storage while RNA is information access and regulation.

RNA has many varieties that differ by size and structure, with smaller forms that are involved in cell regulation and development. Much of the RNA that is transcribed from DNA is processed and modified after it is made.

RNA modifications are chemical structures added on to RNA that regulate information transfer. These RNA modifications are distinct from DNA modifications that are known as epigenetic marks. Whereas DNA modifications can be inherited, RNA modifications arise in response to the current state of the cell. RNA modifications are more dynamic and have more dramatic effects on the structure and function of the cell, including how proteins are made under different cellular conditions.

Under normal conditions, for example, some RNA modification patterns trigger the disposal of RNAs that code for or help decode stress-response proteins. When the cell enters a state of stress, this modification pattern is reprogrammed so these proteins can accumulate and help the cell recover.

Various chemical structures surrounding a three loop structure, with lines pointing to their potential locations

This diagram shows several possible modifications of a type of RNA called tRNA, center.
Mitchener…

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