Untranslatable RNAs are easily synthesized and degraded by living organisms

Difference between RNA and DNA

First, let me explain what RNA is. A similar substance is DNA, but what is the difference between the two?

DNA stands for deoxyribonucleic acid and RNA for ribonucleic acid, and as the names suggest, they have different structures. DNA has adenine (A), guanine (G), thymine (T), and cytosine (C), while RNA has uracil (U) instead of thymine.

So what are the differences in terms of roles? The two roles can be summarized as follows

Thus, although similar in name and structure, their roles in the body are very different.

In addition, there are many types of RNA, and we will discuss the role of each type of RNA in detail.

Protein-coding, translatable RNA 

Translational RNA, also called coding RNA, refers to RNA that "codes" for a protein. A code is a set of three bases in a sequence that designates a single amino acid. In other words, the RNA that has the genetic code to produce an amino acid is translational RNA.

For example, if the RNA sequence is AUG, it encodes the amino acid methionine, and if it is CCG, it encodes the amino acid glycine, and a series of these amino acids become proteins, which are the building blocks of our bodies.

There is only one translational RNA, mRNA (messenger RNA, mRNA).

mRNA (messenger RNA, messenger RNA)

As the name implies, mRNA is RNA responsible for transmitting genetic information.

Based on the nucleotide strand of DNA in the nucleus, RNA that copies the genetic information of DNA is produced by RNA polymerase (RNA synthetase). This is mRNA, and the copying of genetic information is called "transcription. The transcribed mRNA is a genetic code (a three-base cipher, or "codeon") that specifies the type of amino acids as a pair of three bases. Protein synthesis based on this three-combiner code is called "translation.

It is known that only about 2% of the entire human genome is mRNA, which copies the genetic information from DNA. In other words, a very small portion of the genomic DNA becomes a protein. However, starting with the discovery of miRNA (microRNA) in the late 1990s, it was discovered that various types of RNA (non-coding RNA) are synthesized from the non-protein-coding part of the human genome, and it is now known that miRNA has a very important role in the body. These RNAs have been found to play very important roles in living organisms.

Conveniently used non-translatable RNA

Untranslatable RNA is RNA that does not have a three-assembly code, also written as ncRNA (non-coding RNA). As the name suggests, it is RNA that does not code for proteins, i.e., it is active without being translated.

A wide variety of untranslatable RNAs have been found, including tRNA and rRNA, which are representative examples.

tRNA (transfer RNA)

tRNAs, also called transfer RNAs or carrier RNAs, carry amino acids in the cytoplasm to the ribosome when they are made from mRNA. tRNAs have a complementary sequence to the coding sequence of mRNA and also bind to specific amino acids. In other words, when tRNA binds to the coding sequence on mRNA, the genetic code of mRNA is "translated" into amino acids. The synthesized amino acids are linked by peptide bonds to produce proteins, which are the main components of our bodies.

rRNA (ribosomal RNA)

Ribosomal RNA is most abundant in cells and blood and is found on multiple chromosomes and is a component of the ribosome along with proteins. When proteins are synthesized through translation, rRNA is responsible for decoding codons on mRNA and binding tRNA, which has a complementary sequence to the mRNA sequence.

Note that 18S rRNA is sometimes used as an internal standard in genetic analysis because of its high expression level. (S stands for sedimentation coefficient)

microRNA (microRNA, miRNA)

MicroRNAs are short (21-25 nucleotides) single-stranded RNAs that, since their discovery in 2001, have been shown to play a role in skillfully regulating gene expression. It has also been found to be involved in many diseases such as cell cancer, neurological diseases, psychiatric diseases, and vascular diseases, and is attracting attention as a key nucleic acid in the development of biomarkers, companion diagnoses, and wards, as well as in personalized medicine.

In recent years, RNAs in exosomes, which are extracellular vesicles, have been implicated in the mechanisms of cancer growth and metastasis, and the development of new cancer testing and treatment methods targeting miRNAs in exosomes has been active.

The further elucidation and development of RNA in exosomes will shed light on the early detection and treatment of cancer.

lncRNA (long non-coding RNA, long untranslated RNA)

Among untranslated RNAs, lncRNAs are those that are longer than 200 nucleotides. lncRNAs have been actively studied since the discovery of 6,500 in 2009, and we now know that there are more than 20,000 lncRNA genes and transcripts in humans. This is surprisingly more than the number of genes in humans.

Although lncRNAs are known to play important roles in the body, such as building nuclear structures and post-translational modifications, the full picture is still unknown because lncRNAs are often more difficult to analyze due to their lower expression levels than mRNAs. However, lncRNAs are still an area of research with an ever-increasing number of publications.

In addition, lncRNAs have been shown to be involved in X chromosome inactivation.

As human females have XX sex chromosomes and males have XY, the female genome contains twice as many X chromosomes as males. To compensate for this difference in genetic content, the mechanism by which one of the female X chromosomes is inactivated is called X chromosome inactivation. This mechanism involves lncRNAs, and if this X chromosome inactivation does not work properly, it can cause genetic disorders such as Turner syndrome (missing one sex chromosome, such as X0) and Klinefelter syndrome (many sex chromosomes, such as XXY).

The above are just a few examples of diseases in which lncRNAs have been implicated.

Other ncRNAs

Many other types of untranslated RNA have been found.

It has been suggested that snRNAs (small nuclear RNAs) are involved in selective splicing and protection of mRNA precursors. Since many human genetic diseases are known to be caused by dysregulation of selective splicing, research on snRNAs is expected to contribute to the elucidation of the causes of genetic diseases.

Small nucleolar RNA (snoRNA) is involved in making ribosomal RNA and modifying nucleic acids. It binds to proteins and localizes to the nucleolus in the nucleus. snoRNA is also contained in telomerase, which synthesizes telomeres.

In addition to these, there are many other types of untranslatable RNAs, including SRP RNAs called signal recognition complexes, siRNAs used in nucleic acid medicine, and piRNAs that protect genomic DNA in the germline cells. Although it is now known that many of these RNAs are involved in some diseases, the expression levels of many untranslated RNAs are not high, and research to elucidate the entire mechanism is expected.

summary

The following is a summary of the names of RNAs and their roles.

Untranslatable RNAs are easily synthesized and degraded in vivo because they do not encode genes and do not make proteins. Therefore, untranslated RNA plays many roles as a handyman in the body, and recent studies have shown that it is involved in a variety of diseases. The investigation of these mechanisms will help mankind to overcome genetic diseases.

References

• Genetic Engineering from the Basics, Second Edition Takaaki Tamura  (work)
• Higher Education Biology Daiichi Gakushuin