Question

Competing endogenous RNAs act as molecular "sponges." What does this mean, and what do they compete with?

Short answer

What do they compete with? Answer: Competing endogenous RNAs (ceRNAs) are regulatory RNA molecules that play a crucial role in gene expression and regulation by competing for shared microRNA (miRNA) binding sites. They act as molecular "sponges" by soaking up miRNAs, preventing them from binding to their target messenger RNAs (mRNAs), and thus modulating the expression of multiple target genes simultaneously. ceRNAs compete with other RNA molecules, such as mRNAs and long noncoding RNAs (lncRNAs), for the binding of shared microRNA (miRNA) response elements (MREs), indirectly affecting mRNA stability and translation.

Step-by-step solution

Define competing endogenous RNAs (ceRNAs)

Competing endogenous RNAs (ceRNAs) are a type of regulatory RNA molecule found in cells. They play a crucial role in gene expression and regulation by competing for shared microRNA (miRNA) binding sites.

Explain the molecular "sponge" function of ceRNAs

The term "molecular sponge" is used to describe the function of ceRNAs because they can "soak up" miRNAs, preventing them from binding to their target messenger RNAs (mRNAs). By doing so, ceRNAs can modulate the expression of multiple target genes simultaneously. This also indirectly affects the stability and translation of target mRNA molecules.

Describe the competition of ceRNAs

Competing endogenous RNAs (ceRNAs) compete with other RNA molecules, such as messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs), for the binding of shared microRNA (miRNA) response elements (MREs). By sequestering miRNAs from their target mRNAs, ceRNAs can indirectly regulate gene expression levels by affecting mRNA stability and translation. This competition helps to fine-tune and maintain the balance of gene expression within a cell. In summary, competing endogenous RNAs (ceRNAs) act as molecular "sponges" by sequestering miRNAs and preventing them from binding to target mRNA molecules. This results in the modulation of gene expression levels. The competition of ceRNAs occurs with other RNA molecules, such as mRNAs and lncRNAs, for shared miRNA binding sites.

Key concepts

Gene Expression Regulation

Gene expression regulation is a pivotal process in cellular function that ensures genes are expressed at the right time, in the right place, and in the right amount. This process is multi-layered and involves various molecular mechanisms that control how genetic information is translated into functional proteins.

• Transcriptional regulation: At this stage, the synthesis of RNA from DNA is controlled. Transcription factors and complexes interact with promoter regions to either enhance or inhibit the transcription process.
• Post-transcriptional regulation: After transcription, RNA molecules undergo further modifications, including splicing, editing, and transport, which influence their stability and translation efficiency.
• Translational regulation: The translation of mRNA into proteins can be controlled by factors that affect the initiation and elongation phases of translation.
• Post-translational regulation: Once the proteins are synthesized, their function can be modulated by chemical modifications such as phosphorylation, acetylation, and ubiquitination.

Gene expression regulation is crucial for maintaining cellular homeostasis and allows for adaptability in response to environmental changes. Disruptions in this regulatory network can lead to diseases, including cancer.

microRNA

MicroRNAs (miRNAs) are small, non-coding RNA molecules, typically about 20-25 nucleotides in length. They play a significant role in regulating gene expression at the post-transcriptional level.

Biogenesis of miRNA:

• Transcription: miRNA genes are transcribed by RNA polymerase II or III, creating a primary miRNA (pri-miRNA) transcript.
• Processing: This pri-miRNA is processed in the nucleus by the Drosha-DGCR8 complex to form a precursor miRNA (pre-miRNA).
• Export and Maturation: The pre-miRNA is exported to the cytoplasm, where Dicer cleaves it into a mature miRNA duplex.
• Incorporation into RISC: One strand of the duplex is incorporated into the RNA-induced silencing complex (RISC), guiding it to complementary target mRNAs.

Function of miRNA:

• miRNAs regulate gene expression by binding to complementary sequences in target mRNA molecules, leading to their degradation or translational repression.
• They are involved in diverse biological processes, including development, differentiation, proliferation, and apoptosis.
• Deregulation of miRNAs is associated with various diseases, especially cancer, as they can function as oncogenes or tumor suppressors.

Molecular Sponge

The term "molecular sponge" refers to a fascinating regulatory mechanism involving competing endogenous RNAs (ceRNAs). These ceRNAs act like sponges by absorbing microRNAs (miRNAs), thus preventing them from binding to their intended messenger RNA (mRNA) targets.

How CeRNAs Function as Sponges:

• miRNA Sequestration: CeRNAs have binding sites - known as microRNA response elements (MREs) - that are also present on target mRNAs. By binding miRNAs, ceRNAs reduce the miRNA availability for other mRNA molecules.
• Regulatory Balance: This sequestration allows ceRNAs to indirectly control the expression levels of genes targeted by the affected miRNAs, thus contributing to a regulatory network.
• Gene Expression Modulation: By soaking up miRNAs, ceRNAs can stabilize mRNAs, enhancing their translation into proteins, which ultimately alters gene expression dynamics.

Role in Cellular Processes:

• CeRNAs are involved in various crucial processes, including development, differentiation, and disease responses.
• They contribute to the complexity and robustness of gene regulatory networks, ensuring precise control over gene expression in response to cellular conditions.
• Disrupted ceRNA functions have been linked to pathological states, especially cancer, where imbalances in gene regulation often occur.