Unit 4: Post Transcriptional Modifications, Processing of Eukaryotic RNA and Gene Regulation
Exon shuffling
Exon shuffling is a mechanism of gene evolution that rearranges exons within a gene or fuses exons from different genes to create new genes with new functions.
Exons are the coding regions of a gene that are assembled to form mRNA and then translated into protein. Exon shuffling occurs when different exons are recombined in different ways to create new proteins with new structures and functions.
Exon shuffling can occur through multiple mechanisms, including intron-mediated recombination, retrotransposition and trans-splicing. Intron-mediated recombination involves exon recombination within introns, the noncoding regions of DNA located between exons. In retrotransposons, mobile genetic elements that can copy themselves and insert themselves into new sites in the genome, retrotransposons can insert themselves into introns, bringing exon sequences with them. In trans-splicing, exons of different genes are spliced together to form a chimeric mRNA.
Exon shuffling is thought to be a key driver of protein evolution, enabling the rapid generation of new protein functions and the adaptation of organisms to changing environments. It is thought to have played an important role in the evolution of complex biological structures and processes such as the immune system and brain.
Different types of exon shuffling
There are several types of exon shuffling that can occur during genetic evolution. Here are a few examples:
- Exon shuffling within a gene: In this type of exon shuffling, exons within a single gene are rearranged to form new combinations. This can occur through intron-mediated recombination, in which exons are spliced together in a new order, or through exon skipping or inclusion, in which certain exons are removed or retained in the final mRNA transcript.
- Domain shuffling: In domain shuffling, exons encoding functional domains, which are regions of a protein that have a distinct function, are recombined to create new protein structures. This can occur through exon shuffling within a gene or through the fusion of exons from different genes.
- Gene fusion: In gene fusion, exons from different genes are fused together to create a new hybrid gene. This can occur through chromosomal rearrangements or retrotransposition of mobile genetic elements.
- Alternative splicing: Alternative splicing can also be considered a type of exon shuffling, as it involves the recombination of exons in different ways to create different protein isoforms.
These different types of exon shuffling can result in the rapid generation of new protein functions and the evolution of complex biological structures and processes. However, they can also lead to genetic disorders if they disrupt the normal function of essential genes.
RNA editing
RNA editing is a process by which the nucleotide sequence of RNA is altered after transcription, leading to changes in the protein sequence that it encodes. This process can occur in both coding and non-coding regions of RNA, and it can be either site-specific or non-specific.
There are several types of RNA editing, including:
Substitution editing: In substitution editing, a specific nucleotide is changed to a different nucleotide. This can lead to a change in the amino acid sequence of the protein that the RNA encodes.
Insertion/deletion editing: In insertion/deletion editing, nucleotides are added to or removed from the RNA sequence, resulting in a frameshift mutation that alters the protein sequence.
RNA splicing editing: In RNA splicing editing, the splicing of pre-mRNA is altered, leading to the inclusion or exclusion of specific exons in the final mRNA transcript.
RNA editing by base modification: In RNA editing by base modification, the nucleotide bases in RNA are modified chemically. For example, adenosine can be converted to inosine by the action of adenosine deaminase enzymes, which changes the base-pairing properties of the RNA molecule.
RNA editing can occur naturally as a part of gene expression, or it can be induced by external factors such as stress or disease. RNA editing is known to play a role in various biological processes, including the regulation of gene expression, the immune response, and the maintenance of neuronal function in the brain.
Adenosine-to-inosine (A-to-I) editing: This is the most common form of RNA editing in humans. A-to-I editing is catalyzed by the adenosine deaminase acting on RNA (ADAR) enzyme, which converts adenosine to inosine. Inosine is recognized as guanosine by the translation machinery, so this type of editing can change the coding sequence of mRNA and alter the amino acid sequence of the encoded protein.
Cytosine-to-uracil (C-to-U) editing: C-to-U editing is catalyzed by enzymes known as apolipoprotein B mRNA editing enzymes (APOBECs). This type of editing can occur in both coding and non-coding regions of RNA, and can result in changes in protein function or gene regulation.
Adenosine-to-cytosine (A-to-C) editing: A-to-C editing occurs in trypanosomes, a type of protozoan parasite, and involves the conversion of adenosine to inosine, followed by deamination to form a cytosine base.
Uracil-to-cytosine (U-to-C) editing: U-to-C editing occurs in kinetoplastid protozoa, such as Trypanosoma brucei and Leishmania major. In these organisms, most of the mRNAs undergo U-to-C editing, which involves the conversion of uracil to cytosine by a multiprotein editing complex.
Non-coding RNA editing: RNA editing can also occur in non-coding RNAs, such as transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), where it can affect RNA stability, folding, and function.
These different types of RNA editing can have profound effects on gene expression and protein function, and they play important roles in various biological processes, including development, differentiation, and disease.
