Since nucleic acid research burst onto the scientific scene in the 1950s, DNA has been the star of the show. RNA—with the exception of forms such as ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs)—has largely been considered the mere messenger between the all-important DNA and its protein products. Indeed, it was given that very name!
“[DNA] was thought of as the top of the information flow,” says biochemist Julia Salzman of Stanford University. “But that view is starting to become more and more questioned in the community.”
In the last couple of decades, new areas of RNA research have been springing up left and right—each one offering surprising insights into this intriguing molecule. Along with booms in the fields of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and RNA interference (RNAi), researchers have discovered and explored CRISPR RNAs, enhancer RNAs, and, most recently—Salzman’s specialty—circular RNAs.
In addition to discovering and synthesizing new forms of RNA, researchers have uncovered novel functions for previously characterized RNA varieties. Scientists have found that the well-known and thoroughly studied tRNAs, for example, regulate transgenerational inheritance, while some protein-coding mRNAs have been found to double as functional noncoding RNAs.
There is “pervasive moonlighting,” says biologist Mitchell Guttman of Caltech. Even were it possible to operationally define a given subset of RNAs, he added, “that’s only the tip of the iceberg” in terms of their potential functions. “It blows my mind.”
On paper, the chemical structures of RNA and DNA may seem relatively similar, but there are important differences—including RNA’s single-strandedness, its ability to self-fold, and its 2’ hydroxyl group—that give RNA unrivalled functional versatility. “RNA is able to replicate itself, it’s able to serve as an enzyme, and, obviously, it can [encode] proteins,” says Salzman.
“It’s the Jack of all trades,” Guttman agrees.
Keeping up to date with the various new forms and functions of RNA maybe a challenge, but for the inventive researcher, each RNA variant offers a new possibility, adds Guttman.
Just as with antisense RNAs, miRNAs, and CRISPR RNAs, he notes, “I imagine that a lot of what we are discovering about RNA’s new mechanisms and structures can be exploited, allowing us to create new and valuable synthetic tools for research and engineering purposes.”
|RNA Type||Size (nucleotides)||Functions||Taxa|
|Circular RNA (circRNA)||Various||Made from parts or whole mRNAs and lncRNAs; functions for some have been suggested, but are largely unknown.||All eukaryotes|
|Cis-natural antisense transcript (cis-NAT)||Various||Variety of roles in gene regulation, such as RNAi, alternative splicing, genomic imprinting, and X-inactivation (by Xist RNA)||Eukaryotes|
|CRISPR RNA (crRNA)||~100||Resistance to infection by targeting pathogen DNA||Bacteria and archaea|
|Enhancer RNA (eRNA)||~50-2,000||Thought to regulate gene expression||Mammals|
|Guide RNA (gRNA)||~20-50||RNA editing of mitochondrial mRNAs||Kinetoplastid protists|
|Long noncoding RNA (lncRNA)||>200||Some have gene regulatory roles, but many others act in the cytoplasm.||All organisms|
|Messenger RNA (mRNA)||Up to ~100,000||Encodes protein||All organisms|
|MicroRNA (miRNA)||~22||Gene regulation||Most eukaryotes|
|Parasitic RNA||Various||Self-propagation of viruses, viroids, retrotransposons and satellite viruses||Infected eukaryotes and bacteria|
|Piwi-interacting RNA (piRNA)||~26-31||Transposon defense, among other proposed functions||Most animals|
|Ribonuclease MRP (RNA component of mitochondrial RNA processing endoribonuclease; RNase MRP)||277 (human)||rRNA maturation, DNA replication||Eukaryotes|
|Ribonuclease P (RNase P)||341 (H1 RNA component)||A ribozyme that catalyses the maturation of tRNA||All organisms|
|Ribosomal RNA (rRNA)||Small subunit: 1,542 (prokaryote), 1,869 (eukaryote); Large subunit: 2,906 (prokaryote), 5,070 (eukaryote)||Translation||All organisms|
|Short hairpin RNA (shRNA)||~19-29||Gene regulation||Most eukaryotes|
|Signal recognition particle RNA (7SLRNA or SRP RNA)||~300 (eukaryote)||Directs proteins to plasma membrane (prokaryotes) or endoplasmic reticulum (eukaryotes)||All organisms|
|Small Cajal body-specific RNA (scaRNA)||~130-300||Subset of snoRNAs involved in nucleotide modification of RNAs||Eukaryotes|
|Small interfering RNA (siRNA)||~20-25||Gene regulation||Most eukaryotes|
|Small nuclear RNA (snRNA)||~150||Splicing and other functions||Eukaryotes and archaea|
|Small nucleolar RNA (snoRNA)||Most around 70-120||Nucleotide modification of RNAs||Eukaryotes and archaea|
|SmY RNA||~70-90||Trans-splicing (the splicing together of exons from two different mRNA transcripts)||Nematodes|
|Spliced leader RNA (SL RNA)||100 (C. elegans)||Trans-splicing and RNA processing||Lower eukaryotes and nematodes|
|Telomerase RNA component (TERC)||541 (human)||Telomere maintenance during DNA replication||Most eukaryotes|
|Transfer RNA (tRNA)||~76-90||Transfers individual amino acids to the growing peptide chain during translation||All organisms|
|Transfer-messenger RNA (tmRNA)||Most are 325-400||Rescues stalled ribosomes during translation||Bacteria|
|Vault RNA (vtRNA)||~80-150||Noncoding RNAs associated with cytoplasmic vault organelles; function unknown||Eukaryotes|
|Y RNA||~85-112||RNA processing, DNA replication||Animals and bacteria|