The RNA Age: A Primer

Our guide to all known forms of RNA, from cis-NAT to vault RNA and everything in between.

May 11, 2017
Ruth Williams

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