While often pictured as a single-stranded molecule, ribonucleic acid (RNA) can form a double-stranded structure. This formation, known as double-stranded RNA (dsRNA), is a regular feature within biological systems. Structurally distinct from its counterpart, deoxyribonucleic acid (DNA), dsRNA is involved in a range of cellular activities. Its presence is tied to processes from viral replication to the regulation of a cell’s own genes.
When and Where RNA Forms a Double Strand
Double-stranded RNA appears in a cell from two origins: external sources and internal activities. A primary external source is viral infection, as many viruses carry their genetic information as dsRNA. When these viruses infect a cell, they introduce their dsRNA genomes to replicate. Even viruses with single-stranded RNA or DNA genomes can produce dsRNA intermediates during their replication cycle, which the host cell can detect.
Cells also produce their own dsRNA. A single-stranded RNA molecule can fold back on itself, creating short, double-stranded regions called hairpins or stem-loops. These structures are common in messenger RNA (mRNA) and transfer RNA (tRNA) and influence their function. Additionally, dsRNA is a component of the gene-regulating pathway called RNA interference, where it helps control gene expression.
The Unique Structure of Double-Stranded RNA
Double-stranded RNA shares similarities with DNA but has defining characteristics. Like DNA, dsRNA forms a right-handed double helix, but it adopts a configuration known as the A-form helix. This structure is distinct from the B-form helix that DNA assumes. The A-form is shorter and wider, with its base pairs tilted about 20 degrees relative to the helix axis, unlike the B-form’s perpendicular arrangement.
This structural difference arises from the sugar in the RNA backbone. RNA contains ribose sugar, which has a hydroxyl group on the 2′ carbon that prevents it from forming the B-form helix common to DNA’s deoxyribose sugar. The base pairing in dsRNA is also different; Adenine (A) pairs with Uracil (U), while Guanine (G) pairs with Cytosine (C), in contrast to DNA where Adenine pairs with Thymine (T).
The grooves of the dsRNA helix also differ from those of DNA. The A-form helix features a deep, narrow major groove that is largely inaccessible to proteins, and a wide, shallow minor groove. This is the reverse of the B-form DNA helix, which has a wide and accessible major groove. This topography influences how dsRNA interacts with other molecules.
Biological Significance of Double-Stranded RNA
Double-stranded RNA prompts biological responses related to gene regulation and immune defense. One of its primary roles is in RNA interference (RNAi), a mechanism cells use to silence the expression of specific genes. The process begins when a long dsRNA molecule is recognized and cut into smaller, 21-23 base pair fragments by an enzyme called Dicer.
These fragments, known as small interfering RNAs (siRNAs), are loaded into a protein complex called the RNA-Induced Silencing Complex (RISC). The siRNA is unwound, and one strand guides the RISC to a messenger RNA (mRNA) with a complementary sequence. The RISC complex then cuts the target mRNA, leading to its degradation. By destroying the mRNA, the cell prevents it from being translated into a protein, silencing the gene.
Beyond gene regulation, dsRNA signals the innate immune system. The presence of long dsRNA molecules is often a sign of viral infection, which cellular sensors like RIG-I and MDA5 detect. These sensors activate a defensive cascade, leading to the production and release of signaling proteins called interferons.
Interferons travel to neighboring cells, warning them of a viral threat and prompting them to heighten their antiviral defenses. This response includes producing proteins that inhibit viral replication to limit the spread of infection. The cell’s ability to distinguish between its own short dsRNAs and the long dsRNAs from viruses is a part of this defense mechanism.