RNA interference
RNAi is a gene-silencing process using double-stranded RNA.
Last updated
RNA interference (RNAi) is a biological process where RNA molecules suppress gene expression in a sequence-specific manner through double-stranded RNA.[1] Long double-stranded RNA molecules are cut by the Dicer enzyme into short fragments that are roughly 21 to 23 nucleotides in length, which initiates the process.[2] The 2006 Nobel Prize in Physiology or Medicine was awarded jointly to Andrew Fire and Craig Mello for their 1998 RNAi research conducted in the nematode Caenorhabditis elegans.[1]
Quick Facts
- Field
- Molecular biology, genetics
- Known for
- Discovery of RNA interference (RNAi) mechanism
- Key components
- Dicer
- Argonaute 2
- RISC
- siRNA
- miRNA
Facts from the source article.
Key facts and history
RISC binds and degrades target mRNA when the guide strand pairs with a complementary sequence.[2] The initiating dsRNA can be exogenous, from viral infection or laboratory manipulations, or endogenous, as in pre-microRNAs.[3][4] MicroRNAs are genomically encoded non-coding RNAs that help regulate gene expression, particularly during development.[5] Five RNAi medications have been approved by regulatory authorities in the US and Europe as of 2022.[6]
Co-suppression, post-transcriptional gene silencing, and quelling are alternative names that were historically used for RNAi.[1] Many eukaryotes naturally possess the RNAi pathway as an endogenous process.[2] The passenger strand and the guide strand are the two single-stranded RNAs produced when each siRNA is separated.[2] Argonaute 2 is the protein responsible for cleaving the passenger strand, after which that strand undergoes degradation.[2]
The RNA-induced silencing complex (RISC) receives and incorporates the guide strand.[2] According to the miRBase website, as of 2023 there were 28,645 miRNA entries cataloged across 271 biologic species.[7]
What the research sources say
The label for givosiran states it causes degradation of ALAS1 mRNA in hepatocytes through RNA interference, reducing levels of aminolevulinic acid and porphobilinogen.[8] The label for lumasiran states it reduces levels of glycolate oxidase enzyme by targeting HAO1 mRNA through RNA interference.[9] A healthcare professional administers givosiran subcutaneously, and the dosage is calculated according to body weight.[10]
References
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: "RNA interference: concept to reality in crop improvement", Planta, March 2014, p. 543–64; "Antisense RNA gene therapy for studying and modulating biological processes", Cellular and Molecular Life Sciences, March 1999, p. 334–58 (original not read by us) en.wikipedia.org
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: "Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes", Cell, November 2005, p. 607–20 (original not read by us) en.wikipedia.org
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: "Advanced Information: RNA interference", The Nobel Prize in Physiology or Medicine 2006 (original not read by us) en.wikipedia.org
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: "RNA interference: the molecular immune system", Journal of Molecular Histology, August 2004, p. 545–53 (original not read by us) en.wikipedia.org
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: "A developmental view of microRNA function", Trends in Biochemical Sciences, April 2007, p. 189–97 (original not read by us) en.wikipedia.org
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: Adams, "Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis", New England Journal of Medicine, July 5, 2018, p. 11–21; Balwani, "Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria", New England Journal of Medicine, 2020-06-11, p. 2289–2301; Garrelfs, "Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1", The New England Journal of Medicine, 2021-04-01, p. 1216–1226; Adams, "Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with po en.wikipedia.org
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: miRBase.org (original not read by us) en.wikipedia.org
- "LABEL:GIVLAARI- givosiran sodium injection, solution", Daily Med, April 5, 2022. facts only, no text reused. dailymed.nlm.nih.gov
- "LABEL: OXLUMO- lumasiran injection, solution", Daily Med, December 2, 2021. facts only, no text reused. dailymed.nlm.nih.gov
- Wikipedia, "RNA interference" (CC BY-SA 4.0), which cites: "LABEL:GIVLAARI- givosiran sodium injection, solution", Daily Med, April 5, 2022 (we also read that source) en.wikipedia.org
Each numbered sentence above was checked against the source it cites before publication. Sentences citing Wikipedia adapt text from the English Wikipedia article RNA interference (contributors), used under CC BY-SA 4.0; this entry is available under the same licence. Other sources were used for facts only; no text or images are copied from them.
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Sources
Compiled from Wikipedia and the sources listed below. Text from Wikipedia is available under CC BY-SA 4.0; this entry is adapted from it.
- Wikipedia: RNA interference (CC BY-SA 4.0).
- Word definitions: the , each quoted from its Wikipedia article.
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