Question

What is the difference between miRNA and siRNA?

Short answer

miRNAs are endogenous and often inhibit translation, while siRNAs can be exogenous and lead to direct mRNA cleavage.

Step-by-step solution

Define miRNA

MicroRNAs (miRNAs) are small non-coding RNA molecules, typically about 21-23 nucleotides in length. They are derived from the transcription of endogenous genes and function to regulate gene expression by binding to complementary sequences on messenger RNA (mRNA), leading to its degradation or the inhibition of its translation.

Define siRNA

Small interfering RNAs (siRNAs) are also small non-coding double-stranded RNA molecules, approximately 20-25 nucleotides in length. They are usually derived from exogenous sources such as viruses, and they operate by binding to complementary mRNA sequences, leading to its cleavage and degradation, thereby preventing the expression of specific genes.

Compare Biogenesis

miRNAs are processed from primary transcripts (pri-miRNAs) that form hairpin structures within the nucleus, whereas siRNAs are typically formed from longer double-stranded RNA molecules that are cleaved by Dicer enzyme in the cytoplasm.

Compare Mechanism of Action

Both miRNAs and siRNAs guide RNA-induced silencing complexes (RISC) to their target mRNAs. However, miRNAs usually have imperfect base pairing with their target sequences and often inhibit translation, while siRNAs have perfect or near-perfect base pairing, leading to direct cleavage of the mRNA.

Endogenous vs Exogenous

miRNAs are largely endogenous, meaning they are encoded by the organism's own genome, while siRNAs can be endogenous or exogenous, commonly derived from viral infections or experimental introduction.

Key concepts

Gene regulation

Gene regulation is a fundamental process that determines when, where, and how much of a gene's product is made. It’s like a set of instructions telling the body which genes to turn on or off based on various signals and conditions. The human body contains many different cells, each with its own function. Gene regulation ensures that each cell produces specific proteins necessary for its role. This control is critical for development, cell differentiation, and maintaining normal function. Understanding gene regulation also helps in comprehending how cells respond to their environment and how abnormalities in this process can lead to diseases like cancer.

Non-coding RNA

Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins. Though they don’t create proteins, they play essential roles in regulating gene expression and maintaining the cell's health.
Here are two well-known examples of non-coding RNAs:

• microRNAs (miRNAs): These are small RNA molecules, about 21-23 nucleotides long, that regulate gene expression post-transcriptionally by binding to complementary sequences of target mRNAs.
• small interfering RNAs (siRNAs): These are also small RNA molecules, roughly 20-25 nucleotides in length, which originate from exogenous sources like viruses and silence genes by degrading mRNAs.

Their role in gene regulation involves preventing specific genes from making proteins, thereby influencing the cell’s function and behavior.

RNA interference

RNA interference (RNAi) is a biological process where RNA molecules inhibit gene expression or translation. Think of it as a natural defense mechanism against viruses and an essential tool in regulating endogenous genes.
Two primary players in RNA interference are:

• miRNAs: These guide the RNA-induced silencing complex (RISC) to partially complementary mRNA targets, generally leading to translational repression.
• siRNAs: These lead RISC to perfectly complementary mRNA sequences, resulting in mRNA cleavage and degradation.

By harnessing RNAi, scientists can study gene functions and develop therapies for diseases caused by overactive or faulty genes.

mRNA degradation

mRNA degradation is a key process in the regulation of gene expression. It determines the lifespan of the mRNA molecules and thus, how much protein can be produced. If an mRNA is rapidly degraded, only a small amount of protein will be produced, and vice versa.
Here are the main components involved in mRNA degradation:

• miRNAs and siRNAs: These small RNA molecules can directly interact with mRNAs and lead to their degradation.
• Decapping enzymes: These remove the protective cap of mRNA, making it susceptible to degradation.
• Exosomes: These are complexes that degrade RNA molecules in the cytoplasm.

Understanding mRNA degradation is vital for interpreting gene regulation dynamics and developing strategies to manipulate gene expression in research and therapy.

RNA-induced silencing complex

The RNA-induced silencing complex (RISC) is a multiprotein complex that plays a crucial role in gene silencing pathways. RISC is guided by small RNAs like miRNAs and siRNAs to its target mRNA.
Here's how RISC functions:

• Loading: Small RNAs, after being processed, are loaded onto the RISC.
• Binding: RISC, guided by the small RNA, binds to its target mRNA.
• Silencing: Depending on the type of small RNA, RISC either degrades the mRNA (siRNA pathway) or inhibits its translation (miRNA pathway).

The effective action of RISC in silencing gene expression allows cells to fine-tune protein production, maintain homeostasis, and protect against viral infections.