Post-Transcriptional Regulators: Videos & Practice Problems

Post-transcriptional regulation of gene expression involves RNA processing, translation, and degradation. Key processes include splicing, export, and editing of mRNA, which must be properly processed to be translated. Translation can be inhibited by factors like EIFs and translational repressors. Additionally, mRNA degradation rates vary, influenced by poly(A) tail length and mechanisms such as exosomes and nonsense-mediated decay. RNA interference, through siRNAs and microRNAs, further regulates gene expression by targeting mRNAs for degradation, highlighting the complexity of gene regulation beyond transcription.

RNA Regulation

Post-transcriptional regulation is a crucial aspect of gene expression control that occurs after the transcription of DNA into RNA. This regulation primarily involves RNA processing, translation, and degradation, which collectively determine how effectively a gene is expressed.

RNA processing includes several key events such as splicing, export, and editing of the RNA transcript. Properly processed mRNA is essential for its export from the nucleus; improperly processed RNAs remain in the nucleus and are not translated into proteins. This highlights the importance of RNA processing in ensuring that only mature mRNA is available for translation.

Translation itself can also be regulated. Eukaryotic initiation factors (EIFs) play a significant role in this process. These proteins are necessary for translation, but their activity can be inhibited through phosphorylation. When EIFs are phosphorylated, they lose the ability to hydrolyze GTP to GDP, which is critical for promoting translation. Additionally, translational repressors can bind to mRNA and inhibit its translation, further impacting gene expression.

Another important factor in post-transcriptional regulation is the degradation of mRNA. The stability of mRNA varies, with those having shorter poly(A) tails being less stable and more prone to degradation. Several mechanisms are involved in mRNA degradation, including:

• Exosomes: These complexes degrade mRNA from the 3' end to the 5' end using exonucleases.
• P bodies: These are nuclear mRNA processing bodies that also play a role in mRNA degradation.
• Nonsense-mediated decay: This mechanism targets improperly spliced mRNA, particularly when a stop codon is incorrectly placed due to mutations, leading to the degradation of faulty transcripts.

In summary, post-transcriptional regulation encompasses a variety of processes that ensure the proper expression of genes. From RNA processing to translation and degradation, each step is tightly regulated to maintain cellular function and respond to environmental changes. Understanding these mechanisms is essential for comprehending how gene expression is finely tuned within the cell.

RNA Interference

RNA interference (RNAi) is a crucial biological process that regulates gene expression through the action of small regulatory RNAs. One of the primary types of these regulatory RNAs is small interfering RNAs (siRNAs), which play a significant role in protecting cells from viral infections. siRNAs are double-stranded RNA molecules that enter cells and are processed by an enzyme called Dicer. Dicer cleaves the siRNAs into smaller fragments, which are then incorporated into the RNA-induced silencing complex (RISC). Within RISC, one strand of the siRNA is degraded, while the remaining single strand can bind to complementary messenger RNA (mRNA) sequences, leading to their degradation and preventing the expression of viral genes.

In addition to siRNAs, microRNAs (miRNAs) also contribute to gene regulation but differ in their origin. miRNAs are encoded in the genome and are initially transcribed as single-stranded RNAs. After transcription, they form secondary structures known as hairpins or loops. The enzyme Drosha processes these structures, and the resulting miRNAs are exported to the cytosol, where they interact with Dicer to become single-stranded. Similar to siRNAs, the single-stranded miRNAs associate with RISC and bind to the 3' untranslated region (UTR) of target mRNAs, inhibiting their expression through degradation. Each miRNA can regulate approximately 200 different mRNAs, highlighting their extensive role in gene expression regulation.

Beyond siRNAs and miRNAs, other types of regulatory RNAs also exist, such as piwi-interacting RNAs (piRNAs), which suppress transposon activity, and long non-coding RNAs (lncRNAs), which are longer than 200 nucleotides and have various mechanisms of action in gene regulation. Overall, RNA interference serves as a fundamental mechanism by which cells control gene expression, primarily through the degradation of mRNAs by these regulatory RNAs.

Protein Regulation

Protein regulation of gene expression is a crucial aspect of cellular function, influencing how genes are expressed after the initial transcription process. While mRNA regulation post-transcription is a well-known method for controlling gene expression, protein modifications also play a significant role in either activating or suppressing gene activity.

One of the primary ways proteins are modified is through phosphorylation and dephosphorylation, which involve the addition or removal of phosphate groups. These modifications can alter the activity of proteins, thereby impacting gene expression. Additionally, protein cleavage is another modification that can regulate protein function and, consequently, gene expression.

Protein degradation is a vital mechanism for controlling protein levels within the cell. If a protein is degraded, it cannot perform its function, which directly affects gene expression. This process often involves the tagging of proteins with ubiquitin, a small protein that signals for their destruction by the proteasome or lysosomes. A key concept in this context is the degron, a specific region within a protein that determines its stability and degradation rate. For example, proteins with a degron are marked for degradation, leading to a significant decrease in their levels over time, as illustrated by the degradation of the Green Fluorescent Protein (GFP) when a degron is present. In contrast, proteins lacking a degron remain stable and are not degraded as rapidly.

Understanding these mechanisms of protein regulation is essential for comprehending how gene expression is finely tuned in response to various cellular signals and conditions.

Choose all of the following post-transcriptional regulators of gene expression.


a) Micro RNAs
b) siRNAs
c) RNA Polymerase Degradation
d) Exosomes

Post-transcriptional regulation of gene expression involves mechanisms that control the expression of genes after the mRNA has been synthesized. Key players in this process include microRNAs (miRNAs), small interfering RNAs (siRNAs), and exosomes, all of which play crucial roles in modulating mRNA stability and translation.

MicroRNAs are a type of non-coding RNA that function by binding to complementary sequences on target mRNA molecules. This binding results in the formation of double-stranded RNA, which prevents the mRNA from being translated into protein. By silencing specific mRNAs, microRNAs effectively regulate gene expression at the post-transcriptional level.

Similarly, small interfering RNAs are also non-coding RNAs that engage in RNA interference. They achieve this by degrading mRNA molecules, thereby preventing their translation. The action of siRNAs involves the cleavage of mRNA, which ensures that the corresponding protein is not produced, thus serving as another form of post-transcriptional regulation.

Exosomes, which are cellular structures involved in RNA degradation, also contribute to post-transcriptional regulation. They degrade mRNA from the 5' end to the 3' end, effectively dismantling the mRNA and preventing its translation into protein. This degradation process is crucial for controlling the levels of specific mRNAs within the cell.

In contrast, the degradation of RNA polymerase, while it does regulate gene expression, is classified as a pre-transcriptional mechanism. This is because the destruction of RNA polymerase inhibits the synthesis of mRNA altogether, preventing gene expression before it can occur.

In summary, the primary post-transcriptional regulators of gene expression include microRNAs, small interfering RNAs, and exosomes, all of which play vital roles in controlling mRNA stability and translation, thereby influencing protein synthesis and overall gene expression.

When the siRNA interacts with RISC for the first time it is single stranded.

• A. True
• B. False

Answer: (B)

What is the name of the enzyme that cleaves the miRNA in the nucleus before it travels to the cytoplasm to exert its effects?

• A. RISC
• B. Argonaut
• C. DROSHA
• D. RNA Polymerase

Answer: (C)

What is the name of the region on a protein that controls its degradation over time?

• A. Degradation sequences
• B. Ubiquitin
• C. Ubiquitin binding site
• D. Degron

Answer: (D)

All non-coding RNAs are responsible for regulating gene expression.

• A. True
• B. False

Answer: (B)

Here’s what students ask on this topic:

What is post-transcriptional regulation and why is it important?

Post-transcriptional regulation refers to the control of gene expression after an mRNA molecule has been created during transcription. This regulation is crucial because it ensures that mRNA is properly processed, exported, translated, and degraded. Key processes include splicing, export, and editing of mRNA. If mRNA is not correctly processed, it remains in the nucleus and is not translated. Additionally, translation can be inhibited by factors like EIFs and translational repressors. mRNA degradation rates also vary, influenced by poly(A) tail length and mechanisms such as exosomes and nonsense-mediated decay. This regulation allows cells to respond quickly to changes and maintain homeostasis.

How does RNA interference (RNAi) regulate gene expression?

RNA interference (RNAi) regulates gene expression by using small regulatory RNAs, such as siRNAs and microRNAs, to target mRNAs for degradation. siRNAs are double-stranded RNAs that are cleaved by the enzyme Dicer into small fragments. These fragments bind to the RISC complex, which degrades one strand and uses the other to bind complementary mRNA, leading to its degradation. MicroRNAs, encoded in the genome, form hairpin structures that are processed by Drosha and Dicer before associating with RISC. The single-stranded microRNA then binds to the 3' UTR of target mRNAs, inhibiting their expression by promoting degradation. This mechanism is vital for controlling gene expression and protecting cells from viruses.

What role do poly(A) tails play in mRNA stability?

Poly(A) tails play a crucial role in mRNA stability by protecting the mRNA from degradation. The length of the poly(A) tail influences the stability of the mRNA; longer poly(A) tails generally make the mRNA more stable, while shorter tails lead to quicker degradation. This stability is essential for the proper translation of mRNA into proteins. Various mechanisms, such as exosomes and nonsense-mediated decay, target mRNAs with shorter poly(A) tails for degradation. By regulating the length of the poly(A) tail, cells can control the lifespan of mRNA and, consequently, the level of protein production.

What are translational repressors and how do they affect gene expression?

Translational repressors are proteins that inhibit the translation of mRNA into proteins, thereby affecting gene expression. They can bind to specific sequences or structures within the mRNA, preventing the assembly of the translation machinery or the progression of translation. For example, some translational repressors bind to the 5' UTR of mRNA, blocking the binding of ribosomes. Others may interact with EIFs, preventing their function. By inhibiting translation, these repressors ensure that certain proteins are not produced, allowing the cell to finely tune gene expression in response to various signals and conditions.

How does nonsense-mediated decay (NMD) contribute to mRNA regulation?

Nonsense-mediated decay (NMD) is a surveillance pathway that degrades mRNAs containing premature stop codons, preventing the production of truncated, potentially harmful proteins. This process is crucial for maintaining the quality of gene expression. NMD recognizes and targets mRNAs with premature stop codons, often resulting from mutations or improper splicing. The degradation of these faulty mRNAs ensures that only correctly processed and functional mRNAs are translated into proteins. By eliminating defective mRNAs, NMD contributes to the overall fidelity and efficiency of gene expression.