Question

What is RNA interference?

Short answer

RNA interference (RNAi) is a process that inhibits gene expression by neutralizing mRNA molecules using siRNA or miRNA.

Step-by-step solution

Title - Definition

RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules.

Title - Components Involved

The main components involved in RNAi are small interfering RNA (siRNA) and microRNA (miRNA), which bind to the complementary mRNA sequences.

Title - Mechanism

In the RNAi process, double-stranded RNA (dsRNA) is cleaved by the enzyme Dicer into siRNA or miRNA. These small RNA fragments are then incorporated into the RNA-Induced Silencing Complex (RISC).

Title - Targeting mRNA

Once incorporated into RISC, the siRNA or miRNA guides the complex to the complementary mRNA strand. RISC then either cleaves the mRNA, preventing it from being translated into a protein, or represses its translation.

Key concepts

gene expression

Gene expression is a fundamental biological process that allows the information in genes to be used to synthesize proteins, which carry out various functions in the cell.
This process includes two main steps: transcription and translation.
Transcription: DNA is transcribed into messenger RNA (mRNA).
Translation: mRNA is translated to form polypeptides, which fold into functional proteins.
Gene expression is tightly regulated, and disruptions in this process can lead to diseases. RNA interference (RNAi) is one mechanism that cells use to control gene expression at the mRNA level. By degrading mRNA or hindering its translation, RNAi can prevent the production of unwanted proteins.

small interfering RNA

Small interfering RNA (siRNA) plays a crucial role in the RNA interference (RNAi) pathway.
siRNA are short, double-stranded RNA molecules, typically 20-25 base pairs in length.
Here is how siRNA functions:

• Originates from longer double-stranded RNA (dsRNA) molecules.
• Processed by the enzyme Dicer into siRNA fragments.
• Incorporated into the RNA-Induced Silencing Complex (RISC).
• siRNA guides RISC to a complementary mRNA target.
• RISC cleaves the target mRNA, leading to its degradation and preventing the mRNA from translating into a protein.

siRNA provides a highly specific mechanism for silencing genes, making it a powerful tool for studying gene function and potential therapeutic applications.

microRNA

MicroRNA (miRNA) are another type of small RNA involved in RNA interference.
Unlike siRNA, miRNA primarily regulates gene expression post-transcriptionally.
Key points about miRNA:

• Typically 21-23 nucleotides in length.
• Generated from primary miRNA transcripts (pri-miRNA) that form hairpin structures.
• Processed by Dicer before being loaded into the RISC.
• miRNA usually pairs imperfectly with its target mRNA.
• Instead of cleaving mRNA, miRNA often represses translation or causes mRNA destabilization.

miRNAs regulate a broad range of genes and play roles in development, differentiation, and disease. Their imperfect pairing with mRNA allows them to target multiple genes, adding a layer of complexity to gene regulation.

double-stranded RNA

Double-stranded RNA (dsRNA) is the precursor molecule for both siRNA and miRNA.
dsRNA forms when two complementary RNA strands hybridize.
Here's an overview of dsRNA's role in RNA interference:

• dsRNA can originate from viral infections, transposable elements, or synthetic introduction into cells.
• Detected by Dicer, an enzyme that processes dsRNA into smaller fragments.
• Dicer cleaves dsRNA into 20-25 nucleotide siRNA or processes hairpin structures into miRNA.

dsRNA is pivotal because it triggers the RNAi pathway, leading to gene silencing. The effective processing of dsRNA ensures specific targeting of mRNA for regulation or degradation.

RNA-Induced Silencing Complex

The RNA-Induced Silencing Complex (RISC) is integral to the RNA interference mechanism.
It mediates the gene-silencing effects of siRNA and miRNA.
Here’s how RISC operates:

• After Dicer processes dsRNA, siRNA or miRNA is loaded into RISC.
• RISC contains Argonaute proteins, which are essential for its function.
• Guide strands from siRNA or miRNA direct RISC to complementary RNA targets.
• For siRNA, RISC cleaves the target mRNA, leading to its rapid degradation.
• For miRNA, RISC usually represses translation or destabilizes the mRNA.

RISC's ability to silence gene expression at the mRNA level is crucial for regulating genes, defending against viral infections, and maintaining cellular homeostasis.