Roles of RNA in Cells

RNA, in one form or another, touches nearly everything in a cell. RNA carries out a broad range of functions, from translating genetic information into the molecular machines and structures of the cell to regulating the activity of genes during development, cellular differentiation, and changing environments.

RNA is a unique polymer. Like DNA, it can bind with great specificity to either DNA or another RNA through complementary base pairing. It can also bind specific proteins or small molecules, and, remarkably, RNA can catalyze chemical reactions, including joining amino acids to make proteins.

All the RNA in cells are themselves copies of DNA sequences contained in the genes of a cell's chromosomes. Genes that are copied—"transcribed"—into the instructions for making individual proteins are often referred to as "coding genes." The genes that produce RNAs used for other purposes are therefore called "noncoding RNA" genes.

RNA molecules assemble proteins and modify other RNAs

Several key classes of RNA molecules help convert the information contained in the cell's DNA into functional gene products like proteins. Messenger RNAs (mRNAs) are copies of individual protein-coding genes, and serve as an amplified read-out of each gene's nucleic acid sequence. Two key noncoding RNAs participate in the assembly of the proteins specified by mRNAs. Ribosomal RNA (rRNA) constitutes the core structural and enzymatic framework of the ribosome, the machine that synthesizes proteins according to the instructions contained in the sequence of an mRNA. Transfer RNAs (tRNAs) use complementary base pairing to decode the three-letter "words" in the mRNA, each corresponding to an amino acid to be sequentially incorporated into a growing protein chain.

Most RNA molecules, once transcribed from the chromosomal DNA, require structural or chemical modifications before they can function. In eukaryotic cells, mRNAs are assembled from longer RNA transcripts by the spliceosome, which consists of spliceosomal RNAs and protein partners. Spliceosomal RNAs help discard intervening sequences (introns) from pre-mRNA transcripts and splice together the mRNA segments (exons) to create what can be a complex assortment of distinct protein-coding mRNAs from a single gene. Many noncoding RNAs also require post-transcriptional modifications. For instance, ribosomal RNAs receive numerous chemical modifications that are required for proper ribosome assembly and function. These modifications are introduced by protein enzymes in conjunction with specialized noncoding RNAs (called snoRNAs) that base pair with the rRNA and guide the modifying enzymes to precise locations on the rRNA.

Some RNAs possess intrinsic enzymatic activity and can directly catalyze RNA modification reactions. These catalytic RNAs include certain self-splicing RNA transcripts, ribozymes, and RNAse P, an RNA enzyme that trims the ends of tRNA precursors in essentially all cells.

RNA molecules regulate gene expression

Regulation of the production of proteins from coding genes is the basis for much of cellular and organismal structure, differentiation, and physiology. Diverse classes of noncoding RNAs participate in gene regulation at many levels, affecting the production, stability, or translation of specific mRNA gene products.

In prokaryotes (for example, bacteria), small antisense RNAs exert a variety of gene regulatory activities by base pairing specifically to their target mRNAs. Also common in prokaryotes are riboswitches, noncoding RNA sequences that usually function as regulatory domains contained within longer mRNAs. Riboswitches regulate the activity of their host mRNAs by binding to small molecules such as nucleotides or amino acids, sensing the abundance of those small molecules and regulating the genes that make or use them accordingly.

Eukaryotic cells contain thousands of small RNAs associated with various RNA interference (RNAi) pathways. For example, microRNAs (miRNAs) are regulatory RNAs approximately 22 nt long that are produced from longer transcripts that contain a certain kind of double-stranded "hairpin" structure. miRNAs associate with a protein of the Argonaute class, and base-pair specifically to mRNAs to inhibit their stability or translation. There are hundreds of miRNA genes in plants and animals, and each miRNA can regulate the activity of hundreds of protein-coding genes. Therefore, miRNAs individually and collectively have a profound impact on the development and physiology of multicellular eukaryotes.

Small interfering RNAs (siRNAs) are similar in length to microRNAs and are also associated with Argonaute proteins. Unlike miRNAs, which are produced from specific genetic loci that have evolved to regulate mRNAs, siRNAs can derive from essentially any transcribed region of the genome. siRNAs typically act directly upon the locus from which they are produced. So, siRNAs occur in cells where genes are under ongoing self-regulation by RNAi.
A major role for certain classes of small noncoding RNAs is defense of the cell against viruses, transposons, and other nucleic acid sequences that pose a potential threat to cellular homeostasis or genome stability. The response of some cells against viral infection includes the production of siRNAs complementary to the virus. Many endogenous siRNAs in eukaryotic cells specify the silencing of transposons and repeat sequences that are already resident in the genome. Similarly, in animals the Piwi-associated RNAs (piRNAs) promote genome integrity by silencing transposons and repeat sequences.

Another class of regulatory RNA consists of diverse kinds of longer noncoding transcripts that generally function to regulate the expression of distant genetic loci, often by suppressing or promoting their transcription. For example, the rox RNAs of the fruit fly seems to facilitate the remodeling of chromosome structure to allow the male X chromosome to be transcribed at twice the rate as a single X chromosome in females, which have two X's. Similarly, the Xist RNA in mammals helps inactivate one of the two X chromosomes in females, allowing males and females to have equivalent levels of gene expression from the X chromosome. Xist is one example of a broader class of very versatile regulatory RNAs known as long intergenic noncoding RNAs (lincRNAs). lincRNAs can act as scaffolds for the assembly of complexes of transcriptional regulatory proteins, and can facilitate the recruitment of defined combinations of protein regulators to specific genes.