What is RNA (Ribo-nucleic acid)

RNA is not just DNA's little-known cousin, it plays a central role in transforming genetic information into body proteins. This extraordinary molecule also carries the genetic instructions of many viruses, which may help life begin.

Central Dogma

RNA (abbreviation for ribonucleic acid) and DNA (abbreviation for deoxyribonucleic acid) together constitute nucleic acid, one of three to four major macromolecules considered essential to life. (The others are proteins and lipids. Many scientists also include carbohydrates in this group.) Macromolecules are very large molecules, usually composed of repetitive subunits. RNA and DNA are composed of subunits called nucleotides.

These two nucleic acids combine to produce a protein. The process of using the genetic information in nucleic acids to make proteins is so important to live that biologists call it the central law of molecular biology. Dogma describes the flow of genetic information in an organism. DNA information is written or transcribed into RNA information, and RNA information is written or translated into protein. RNA is fundamentally a biological molecule that connects DNA and protein.

RNA alphabet

The ability of RNA and DNA to store and replicate information depends on the repeating nucleotide subunits of the molecule. Nucleotides are organized in specific sequences and can be read like letters in words. Every nucleotide has three main parts: a sugar molecule, a phosphate group, and a cyclic compound called a nucleobase or base. Sugars from different nucleotide units are connected by phosphate bridges to form repeating polymers of RNA or DNA molecules—like a necklace of sugar beads linked together by phosphate chains.

As described by the National Human Genome Research Institute, nucleobases linked to sugar constitute the sequence information needed to construct proteins. RNA and DNA each have a set of four bases: adenine, guanine, cytosine, and thymine in DNA, and uracil in RNA exchanges for thymine. The four bases form the alphabet of molecules, so they are represented by letters: A for adenine, G for guanine, and so on.

But RNA and DNA can do more than just encode letter sequences; they can also copy them. This is effective because bases on one RNA or DNA string can stick to bases on another string, but only in a very specific way. The bases are only connected to complementary partners: C to G and A to U in RNA (or A to T in DNA). Therefore, DNA serves as a template to transcribe RNA molecules, and it reflects the DNA sequence—the record that encodes it.

A type of RNA called messenger RNA (mRNA) uses this replication function to transfer genetic data from DNA to ribosomes, which are the protein-producing components of cells. The ribosome reads the mRNA sequence to determine the order in which protein subunits (amino acids) should be added to the growing protein molecule.

Two other types of RNA complete this process: transfer RNA (tRNA) brings amino acids specified by mRNA to the ribosome, and ribosomal RNA (rRNA), which makes up most of the ribosome, connects the amino acids together.

RNA as an enzyme

Scientists believe that the central law activity of RNA is the core of the molecular definition. But since biologists Sidney Altman and Thomas R. Cech discovered in the 1980s that RNA can function like a protein, the idea of what RNA is and what it can do has greatly expanded. (Researchers won the 1989 Nobel Prize in Chemistry for their discoveries.)

Proteins are the key components of most chemical reactions in the body. They are partly attributed to the amazing variety of shapes or conformations that these molecules can achieve as enzymes. (Enzymes are proteins that promote and catalyse chemical reactions.) Unlike DNA, RNA can also be deformed to a certain extent to be used as an RNA-based enzyme or ribozyme. Biologist Merlin Crossley wrote in The Dialogue that part of the greater flexibility of RNA than DNA comes from the extra oxygen on RNA ribose, which makes the molecule less stable. The deoxygenation in deoxyribose refers to the 1-oxygen deficiency of DNA.

According to some researchers, the most important RNA-based catalytic activity occurs in the ribosome, where rRNA, a ribozyme, mediates the addition of amino acids to growing proteins. Other ribozymes include small nuclear RNA (snRNA), which splices mRNA into a usable form, and M1 RNA, which is one of the first known ribozymes, which similarly cuts bacterial tRNA.

RNA's regulatory zoo

In the past 30 years, the number of known types of RNA has skyrocketed because researchers have discovered a group of RNAs with completely different roles: regulating genes. There is a whole set of RNAs that play a key regulatory role, affecting the expression and speed at which genes are expressed.

In a review published in the International Journal of Biomedical Sciences in 2017, researchers wrote that in recent years, few biological fields have changed as radically as RNA molecular biology, which is largely due to A small regulatory RNA. The author writes that the most important ones are short interfering RNA (siRNA), micro RNA (miRNA) and piwi interacting RNA (piRNA).

siRNA and miRNA silence genes by appending complementary sequences to the mRNA. Regulatory RNA then activates protein complexes that can cleave mRNA or prevent its translation, as described in a review published in the journal "Contemporary Genomics" in 2010. According to a review published in Cell in 2009, siRNAs target invasive genetic material, such as viral DNA, while miRNAs regulate the organism’s own genes. According to a review published in Development magazine in 2014, piRNAs perform similar silencing, but operate exclusively in sex cells, targeting mobile genetic material sites called transposable factors that can mutate genes.

Other regulatory RNA players include heavier long non-coding RNA (lncRNA), which affects genes by linking to DNA and protein complexes called chromatin, as described in a 2019 review in the Non-coding RNA Journal. lncRNA can activate or inactivate parts of the chromatin, packaging DNA into a compact form in the cell so that the gene expression or inhibition of the chromatin. According to a 2020 review in the Journal of Frontiers in Cell and Developmental Biology, enhancer RNA, contrary to most of the above effects, increases the expression of certain genes through ununderstood mechanisms.

Other RNA types have also appeared in other organisms. For example, bacterial hosts are similar to miRNA and siRNA and are called small RNA regulators (sRNA). Part of the gene-editing CRISPR-Cas9 system found in bacteria and archaea also relies on RNA, which binds to the so-called CRISPR DNA sequence that recognizes invaders.

The World of RNA

The versatility of RNA in function and form helped spark the idea known as the RNA World Hypothesis. Organisms rely on an extremely complex system composed of DNA, RNA, and protein to transmit genetic information. Scientists have long wondered how this system emerged in early life forms. RNA provides a logical answer. The molecule can both store genetic information and catalyse reactions, suggesting that early simple organisms may only rely on RNA.

This is a hybrid. Therefore, as a start, this is perfectly reasonable. In addition, he said, the glycosylated ribose of RNA always appears first in organisms because it is easier to manufacture. Then deoxyribose is produced from ribose. So this means that in life, you first have ribose, RNA, and then DNA.

Starting from simpler RNA, more complex life may emerge, evolve more stable DNA as a long-term library, and develop protein as a more effective catalyst.

Why RNA at all?

In the process from DNA to protein, RNA essentially acts as a middleman, so why not eliminate the RNA middleman and go directly from DNA to protein? He said that simple life forms, such as DNA viruses, do just that. Similarly, some of the most notorious viruses—HIV, the common cold virus, influenza, and COVID-19—have all their genetic information hidden in RNA, without a DNA precursor.

However, more complex organisms require more gene regulation, he said. Therefore, most of their genomes do not code for proteins but instead code for parts of the genome that regulate other sequences. For example, the promoter can turn genes on or off. You don’t want to convert the 3 billion base pairs of the human genome into protein sequences. It would be a huge waste to spend cellular resources on so many sequences that cannot encode the required human protein. RNA makes it possible to transcribe only the protein-coding positions of the gene sequence into mRNA intermediates.

In addition, mRNA provides a convenient way to fine-tune gene output. RNA is a photocopy of DNA, and the RNA Association says it is a non-profit organization that promotes the sharing of RNA research. When a cell needs to produce a certain protein, it produces multiple copies of that DNA in the form of messenger RNA. Therefore, RNA expands the amount of a given protein that can be produced at one time.

Once again, the ability of RNA to amplify is due to the flexibility of the molecule. Because RNA can be folded into various shapes, it can generate the mRNA and tRNA conformations needed to run a photocopier. DNA cannot do this.

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