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Ch. 18 - Post-transcriptional Regulation in Eukaryotes
Klug - Concepts of Genetics  12th Edition
Klug12th EditionConcepts of Genetics ISBN: 9780135564776Not the one you use?Change textbook
Chapter 18, Problem 6

Explain how a tissue-specific RNA-binding protein can lead to tissue-specific alternative splicing via splicing enhancers or splicing silencers.

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1
Understand that alternative splicing is a process where different combinations of exons are joined together to produce multiple mRNA variants from a single gene, allowing for tissue-specific protein diversity.
Recognize that RNA-binding proteins (RBPs) can influence splicing by binding to specific sequences on the pre-mRNA called splicing enhancers or splicing silencers, which are regulatory elements that promote or inhibit the use of nearby splice sites.
Identify that tissue-specific RNA-binding proteins are expressed only in certain cell types or tissues, so their presence or absence determines which splicing enhancers or silencers are active in that tissue.
Explain that when a tissue-specific RBP binds to a splicing enhancer (often called an exonic splicing enhancer, ESE), it recruits the splicing machinery to promote inclusion of a particular exon in the mature mRNA in that tissue.
Conversely, when the RBP binds to a splicing silencer (such as an intronic splicing silencer, ISS), it blocks the splicing machinery from recognizing a splice site, leading to exclusion of that exon in the tissue where the RBP is present.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Alternative Splicing

Alternative splicing is a process by which different combinations of exons are joined together from a single pre-mRNA transcript, resulting in multiple mRNA variants and protein isoforms. This mechanism increases proteomic diversity and allows cells to produce tissue-specific proteins by including or excluding certain exons.
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RNA-Binding Proteins and Tissue Specificity

RNA-binding proteins (RBPs) recognize specific RNA sequences or structures and regulate splicing decisions. Tissue-specific RBPs are expressed only in certain cell types, enabling them to influence splicing patterns uniquely in those tissues by binding to regulatory elements on the pre-mRNA.
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Splicing Enhancers and Silencers

Splicing enhancers and silencers are short RNA sequence motifs that promote or inhibit the use of nearby splice sites. RBPs bind to these elements to either recruit or block the spliceosome, thereby modulating exon inclusion or skipping in a tissue-specific manner.
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