Subgenomic RNA refers to smaller RNA molecules produced from a larger, full-length RNA genome. These segments are particularly relevant in virology. Their existence allows for complex regulation of gene expression, playing a part in how some viruses multiply and interact with their host cells. Understanding these molecules offers insights into how viruses function and replicate.
What is Subgenomic RNA?
Subgenomic RNA (sgRNA) is an RNA molecule shorter than the complete genomic RNA from which it originates. They are commonly found in positive-strand RNA viruses, including large families such as coronaviruses and arteriviruses.
Unlike full genomic RNA, which contains instructions for viral replication machinery, sgRNAs usually encode specific viral proteins. They carry genetic information for viral structural proteins (e.g., spike, envelope, membrane, nucleocapsid) and various accessory proteins.
Though a single sgRNA might contain multiple coding regions (open reading frames or ORFs), typically only the ORF closest to the 5′ end is translated into protein. This makes them functionally monocistronic, even if genetically polycistronic.
How Subgenomic RNA is Formed
The production of subgenomic RNA in many viruses, particularly coronaviruses and arteriviruses, occurs through discontinuous transcription. This mechanism involves the viral RNA-dependent RNA polymerase (RdRp) engaging in a precise “template switching” during negative-strand RNA synthesis.
The polymerase begins transcribing the genomic RNA, pausing at specific internal body transcription-regulating sequences (TRS-B). At these TRS-B sites, the nascent negative-strand RNA detaches from the genomic template and reattaches to a complementary leader transcription-regulating sequence (TRS-L) at the 5′ end of the viral genome.
This jump allows the polymerase to continue synthesis, incorporating the leader sequence onto the new RNA molecule. The result is a nested set of sgRNAs, all sharing the same 5′ leader sequence and being co-terminal at their 3′ end with the genomic RNA. This intricate process, often within specialized double-membrane vesicles inside the host cell, ensures the precise and regulated production of viral transcripts.
Roles of Subgenomic RNA
Subgenomic RNA primarily facilitates the expression of specific viral genes, particularly those encoding structural and accessory proteins. These proteins differ from replicase proteins, translated directly from full-length genomic RNA.
By producing multiple sgRNAs, viruses regulate the quantity and timing of protein syntheses. For example, structural proteins (e.g., spike, envelope, membrane), needed in large amounts for new virus assembly, are efficiently produced from sgRNAs.
This regulated expression allows viruses to manage their limited genetic material effectively, ensuring proteins are available at appropriate stages of the viral life cycle. sgRNAs also coordinate the assembly of new viral particles. Their production and translation into proteins contribute to progeny virion formation, making them a key component of viral propagation.
Subgenomic RNA in Viral Life Cycles and Disease
Subgenomic RNA plays a role in the life cycles and disease progression of many viruses, notably coronaviruses and arteriviruses. These viruses depend on sgRNA production for their replication and pathogenesis.
The synthesis and translation of sgRNAs contribute to various stages of the viral life cycle, including new virus particle assembly and release from infected cells. For instance, in SARS-CoV-2, proteins encoded by sgRNAs, such as the nucleocapsid protein, are responsible for packaging the genomic RNA into new virions.
Understanding subgenomic RNA dynamics is valuable for diagnostics and antiviral strategies. The presence of sgRNA in infected cells indicates active viral replication, distinguishing active infection from residual viral material.
For example, detecting SARS-CoV-2 sgRNA helps assess infection stage and guide patient management. Targeting conserved sequences within sgRNAs, such as the 5′ untranslated region leader sequence, has shown promise in inhibiting viral gene expression and replication, offering potential avenues for antiviral drug development.