Non-coding RNA

Non-coding RNA, often called ncRNA, refers to functional RNA molecules that are not translated into proteins. In the central flow of genetic information, most RNA acts as a middle step to build proteins. However, ncRNA molecules perform various other tasks within the cell. The DNA sequences that produce these functional molecules are known as RNA genes.

While the exact number of non-coding RNAs in the human genome is unknown, bioinformatic studies suggest there are thousands of different transcripts. There is still a scientific debate regarding their purpose. Some researchers view much of this transcription as "junk RNA" or accidental errors. Others argue that many of these transcripts have essential functions that we have yet to fully discover.

Many essential ncRNAs are involved in the process of translation, which is how cells build proteins. A major player here is ribosomal RNA, or rRNA. These molecules are part of the ribosome, which acts as a factory for protein synthesis. In eukaryotes, ribosomes contain four different types of ncRNA, while prokaryotes use three. The rRNA molecules actually catalyze the translation of nucleotide sequences into proteins. Another group, transfer RNA, or tRNA, serves as an adaptor molecule. It sits between the messenger RNA (mRNA) and the growing protein chain.

Other ncRNAs act as guides or processors for different cellular components. Small nucleolar RNAs, or snoRNAs, are found in archaea and eukaryotes. They guide the chemical modification of rRNA, tRNA, and small nuclear RNAs (snRNAs). Another molecule, RNase P, is a ubiquitous ribonucleoprotein that matures tRNA sequences. It does this by cleaving the 5'-leader elements from precursor-tRNAs. Additionally, the spliceosome is a complex involved in RNA splicing. This process removes intron sequences to create mature mRNA. The bulk of the spliceosome is actually made of ncRNA, such as U1, U2, U4, U5, and U6.

The history of discovering these molecules spans over a century. Friedrich Miescher first discovered nucleic acids in 1868. By 1939, scientists had linked RNA to protein synthesis. In the 1960s, researchers focused on characterizing tRNA using baker's yeast. To obtain just 1g of purified alanine tRNA, scientists had to use 140kg of commercial yeast. They used enzymes like pancreatic ribonuclease to digest the RNA into fragments for sequencing. In 1974, independent groups used X-ray crystallography to finalize the "cloverleaf" structure of tRNA. Later, the discovery of the RNAi mechanism led to a Nobel Prize for Craig C. Mello and Andrew Fire in 2006.

Non-coding RNAs also play massive roles in gene regulation through trans-acting and cis-acting mechanisms. Trans-acting ncRNAs, like microRNAs (miRNA), can regulate gene expression from a distance. A single miRNA molecule can reduce the expression levels of hundreds of different genes. This happens through partial complementarity to mRNA molecules. In terms of genome defense, piRNAs form complexes with Piwi proteins to silence certain genetic elements. Bacteria also use a system called CRISPR. These are DNA repeats separated by spacers that help protect the cell from viral infection.

Some ncRNAs work much closer to the genes they influence, known as cis-acting regulation. For example, riboswitches are RNA elements that can directly bind to small target molecules. This binding changes the activity of the gene. Other elements, like iron response elements (IRE), are found in the untranslated regions of mRNA. When iron levels are low, specific proteins bind to these elements to control metabolism. In mammals, the long ncRNA known as Xist is vital for chromosome structure. It is responsible for X-chromosome inactivation in placental mammals by forming Barr bodies.

Finally, ncRNAs are critical for maintaining the stability of our genetic material. Telomerase is a specialized enzyme that helps protect the ends of chromosomes. These ends are called telomeres. Telomerase is a reverse transcriptase that carries a specific Telomerase RNA. This RNA acts as a template to add DNA sequence repeats to the telomeres. This process is necessary because telomeres shorten every time a cell replicates. Without these molecular tools, the complex instructions within our DNA could not be safely managed or executed by the cell.