Ribosomal frameshifting mRNA a reoccurring question

By SWA

Ribosomal frameshifting is a molecular mechanism used by cells to produce different proteins from a single strand of messenger RNA (mRNA). It plays a crucial role in the regulation of gene expression and is especially notable in viral protein synthesis. Here's an overview of how it works:

  1. Basic Concept of Translation and Reading Frame: Normally, ribosomes translate mRNA into proteins by reading nucleotides in groups of three, called codons. Each codon corresponds to a specific amino acid. The sequence of reading these codons is known as the "reading frame." There are three possible reading frames for any mRNA, depending on where the ribosome starts translation.

  2. What is Frameshifting? Ribosomal frameshifting occurs when the ribosome shifts from one reading frame to another while translating mRNA. This shift can be either forward (to the right) or backward (to the left), and it usually involves moving one or two nucleotides. This shift changes the set of codons that are read downstream of the shift site, leading to a different sequence of amino acids in the produced protein.

  3. Stimuli for Frameshifting: Frameshifting is not random but is stimulated by specific signals in the mRNA. These signals include:

    • Slippery Sequences: A short sequence of nucleotides in the mRNA where the ribosome can slip back or forward. These sequences often have a pattern of repeated nucleotides.
    • RNA Secondary Structures: Structures like hairpins or pseudoknots in the mRNA can cause the ribosome to pause or slow down, increasing the likelihood of frameshifting.

  4. Role in Viral Replication: Many viruses, including HIV and coronavirus, rely on ribosomal frameshifting to produce essential proteins for their replication. In these viruses, frameshifting allows the production of different proteins from the same RNA segment, an efficient mechanism given their small genome size.

  5. Regulation and Implications: Ribosomal frameshifting is a tightly regulated process. Its efficiency can be influenced by various factors, including the sequence of the mRNA and the cellular environment. Abnormal frameshifting can lead to diseases, including cancer. Understanding and manipulating frameshifting has potential applications in developing antiviral therapies and understanding genetic diseases.

In summary, ribosomal frameshifting is a sophisticated mechanism that expands the genetic coding capacity of an mRNA molecule, allowing the production of multiple different proteins from a single RNA sequence. It's a testament to the complexity and adaptability of cellular and viral genetic mechanisms.

 Generated by DALL·E

An educational illustration that explains the concept of ribosomal frameshifting.
The image shows a ribosome translating mRNA into a protein. It highlights key features such as the 'slippery sequence' and a 'pseudoknot' structure in the mRNA. The ribosome is depicted in two positions: one before and one after the shift, to demonstrate the change in the reading frame.
This change aligns the ribosome with different sets of codons, illustrating the frameshifting process.
The elements are clearly labeled for better understanding.

Related papers:
N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting

Modified messenger-RNA components alter the encoded protein

 

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