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How does alternative splicing of pre-mRNA molecules affect the final protein product? Provide an explanation with examples.

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Alternative splicing is a crucial process that occurs during the maturation of pre-messenger RNA  pre-mRNA  molecules in eukaryotic cells. It allows for the generation of multiple, distinct mature mRNA molecules from a single pre-mRNA molecule, which in turn leads to the production of different protein isoforms. This process significantly contributes to the diversity of proteins and their functions within an organism.During alternative splicing, different combinations of exons  coding regions  are joined together, and introns  non-coding regions  are removed from the pre-mRNA molecule. This results in the generation of multiple mRNA molecules with different exon compositions. Each of these mRNA molecules can then be translated into a distinct protein isoform, which may have different functions, structures, or subcellular localizations.There are several types of alternative splicing events, including:1. Exon skipping: In this event, one or more exons are excluded from the final mRNA molecule. This can lead to the production of a protein with a missing or altered functional domain.Example: The human gene encoding the protein dystrophin undergoes exon skipping, leading to the production of different dystrophin isoforms. Mutations in this gene can cause Duchenne muscular dystrophy, a severe muscle-wasting disease.2. Alternative 5' or 3' splice site selection: In this event, different splice sites at the 5' or 3' end of an exon are used, leading to the inclusion or exclusion of specific nucleotide sequences in the final mRNA molecule. This can result in proteins with altered N- or C-termini.Example: The human gene encoding the protein tropomyosin undergoes alternative 5' splice site selection, leading to the production of different tropomyosin isoforms with different N-terminal sequences. These isoforms have distinct functions in muscle contraction and cytoskeleton organization.3. Intron retention: In this event, one or more introns are retained in the final mRNA molecule. This can lead to the production of a protein with an altered sequence or premature termination due to the presence of a stop codon within the retained intron.Example: The human gene encoding the protein fibroblast growth factor receptor 2  FGFR2  undergoes intron retention, leading to the production of different FGFR2 isoforms. These isoforms have distinct roles in cell signaling and development.4. Mutually exclusive exons: In this event, two or more exons are spliced in a mutually exclusive manner, meaning that only one of the exons is included in the final mRNA molecule. This can lead to the production of proteins with distinct functional domains.Example: The human gene encoding the protein CD44 undergoes mutually exclusive exon splicing, leading to the production of different CD44 isoforms. These isoforms have distinct roles in cell adhesion, migration, and signaling.In summary, alternative splicing of pre-mRNA molecules plays a critical role in generating protein diversity within an organism. By producing multiple mRNA molecules with different exon compositions from a single pre-mRNA molecule, alternative splicing allows for the synthesis of distinct protein isoforms with diverse functions, structures, and subcellular localizations.
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