RNA-Based Regulation
RNA is not only a messenger between gene and protein but a regulator in its own right, with small and long non-coding RNAs silencing genes, fine-tuning expression, and guiding the machinery that shapes the genome's output.
Definition
RNA-based regulation is the control of gene expression by RNA molecules, particularly non-coding RNAs such as microRNAs and small interfering RNAs, which silence or fine-tune target genes by base-pairing with their transcripts or guiding regulatory complexes.
Scope
This topic covers RNA interference and the small RNAs that mediate it, microRNAs and their tuning of messenger-RNA stability and translation, small interfering RNAs and gene silencing, the broad roles of long non-coding RNAs, and the use of these pathways as research tools and therapeutics. It treats post-transcriptional and RNA-guided regulation; transcription-level control and chromatin-based control are covered in the adjacent topics.
Core questions
- How does double-stranded RNA trigger sequence-specific gene silencing?
- How do microRNAs regulate messenger-RNA stability and translation?
- What distinguishes small interfering RNAs from microRNAs?
- What roles do long non-coding RNAs play in regulation?
Key concepts
- RNA interference
- MicroRNAs and translational repression
- Small interfering RNAs and gene silencing
- Long non-coding RNAs
- RNA-based tools and therapeutics
Mechanisms
Double-stranded RNA is processed into short guides that load into silencing complexes; these complexes find complementary messenger RNAs and either cleave them or block their translation, and partial complementarity by microRNAs tunes expression more gently, while some long non-coding RNAs scaffold or recruit regulatory proteins to specific loci.
Clinical relevance
RNA interference is a routine laboratory tool for knocking down genes, and RNA-based drugs, including small interfering RNA therapeutics and antisense oligonucleotides, are now approved for several diseases, while dysregulated microRNAs serve as cancer biomarkers.
History
Ambros and colleagues discovered the first microRNA in the early 1990s, and Fire and Mello's 1998 demonstration that double-stranded RNA potently silences matching genes in the worm revealed the RNA interference pathway, work recognized by the 2006 Nobel Prize and rapidly adopted across biology.
Key figures
- Andrew Fire
- Craig Mello
- Victor Ambros
Related topics
Seminal works
- fire1998
Frequently asked questions
- What is RNA interference?
- RNA interference is a natural pathway in which double-stranded RNA is processed into short guides that direct the destruction or silencing of messenger RNAs with a matching sequence, switching off the corresponding gene.
- What do microRNAs do?
- MicroRNAs are short non-coding RNAs that base-pair with target messenger RNAs and reduce their stability or translation, allowing the cell to fine-tune the levels of many genes at once.