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How does alternative splicing affect the structure and function of RNA transcripts in eukaryotic cells? Provide examples of proteins that result from alternative splicing and explain how their functions differ from the unspliced form.

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ago by (450 points)
Alternative splicing is a crucial post-transcriptional regulatory mechanism that occurs in eukaryotic cells. It allows a single gene to produce multiple protein isoforms by selectively including or excluding specific exons  coding regions  from the pre-mRNA molecule during the splicing process. This process significantly increases the diversity of proteins that can be produced from a limited number of genes, thus contributing to the complexity of eukaryotic organisms.The structure and function of RNA transcripts are affected by alternative splicing in several ways:1. Protein domain variation: Alternative splicing can lead to the inclusion or exclusion of specific protein domains, which can alter the protein's function, localization, or interaction with other proteins.2. Regulatory element variation: Alternative splicing can introduce or remove regulatory elements, such as miRNA binding sites or protein binding sites, which can affect the stability, localization, or translation efficiency of the mRNA molecule.3. Coding sequence variation: Alternative splicing can cause frame-shifts or premature stop codons, which can lead to the production of truncated proteins with altered functions or non-functional proteins that are targeted for degradation.Examples of proteins that result from alternative splicing and their functional differences:1. Troponin T  TnT : Troponin T is a component of the troponin complex, which regulates muscle contraction in response to changes in intracellular calcium levels. Alternative splicing of the TnT gene generates different isoforms that are expressed in a tissue-specific manner. For example, the cardiac TnT isoform is expressed in the heart, while the skeletal TnT isoforms are expressed in skeletal muscles. These isoforms have different sensitivities to calcium, which allows for the fine-tuning of muscle contraction in different tissues.2. Calcitonin gene-related peptide  CGRP  and calcitonin: The CALC1 gene can undergo alternative splicing to produce two different peptides with distinct functions. Calcitonin is a hormone involved in calcium homeostasis and bone metabolism, while CGRP is a potent vasodilator involved in pain transmission and migraine. The alternative splicing event that generates these two peptides involves the inclusion or exclusion of specific exons, leading to the production of proteins with different C-terminal sequences and functions.3. Bcl-x: The Bcl-x gene encodes for two isoforms, Bcl-xL and Bcl-xS, which are generated through alternative splicing. Bcl-xL is an anti-apoptotic protein that promotes cell survival by inhibiting the release of cytochrome c from mitochondria, while Bcl-xS is a pro-apoptotic protein that promotes cell death by antagonizing the function of Bcl-xL. The balance between these two isoforms plays a critical role in determining cell fate and is often dysregulated in cancer.In conclusion, alternative splicing is a vital mechanism that contributes to the diversity and complexity of eukaryotic proteomes. It can affect the structure and function of RNA transcripts and proteins by generating isoforms with distinct properties, which can have significant implications for cellular processes and organismal development.
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