Incorrectly spliced RNAs often lead to human pathologies. Scientists have examined cancer cells for splice-specific changes and found that many of the changes disrupt tumor-suppressor gene function [Xu and Lee (2003). Nucl. Acids Res. 31:5635–5643]. In general, what would be the effects of splicing changes on these RNAs and the function of tumor-suppressor gene function? How might loss of splicing specificity be associated with cancer?

Verified step by step guidance

1. Step 1: Understand the role of splicing in gene expression. Splicing is the process by which introns are removed from pre-mRNA transcripts and exons are joined together to form mature mRNA, which is then translated into functional proteins.
2. Step 2: Recognize that tumor-suppressor genes produce proteins that regulate cell growth and prevent uncontrolled cell division, thus protecting against cancer development.
3. Step 3: Consider how incorrect or altered splicing can lead to the production of abnormal mRNAs that may encode truncated, nonfunctional, or even harmful proteins, or may trigger mRNA degradation through nonsense-mediated decay.
4. Step 4: Analyze how disruption of tumor-suppressor gene function due to splicing errors can impair the cell's ability to control growth and repair DNA damage, thereby promoting tumor formation and progression.
5. Step 5: Connect the loss of splicing specificity to cancer by explaining that widespread splicing errors can lead to a reduction in functional tumor-suppressor proteins, contributing to the accumulation of mutations and uncontrolled cell proliferation characteristic of cancer cells.

Key Concepts

RNA Splicing and Alternative Splicing

RNA splicing is the process by which introns are removed from pre-mRNA and exons are joined to form mature mRNA. Alternative splicing allows a single gene to produce multiple protein variants by including or excluding certain exons. Errors in splicing can lead to abnormal mRNA transcripts that may produce dysfunctional or truncated proteins.

Tumor-Suppressor Genes and Their Function

Tumor-suppressor genes encode proteins that regulate cell growth and prevent uncontrolled proliferation. Proper function of these genes is critical for preventing cancer. Disruption of their expression or function, such as through splicing errors, can impair their ability to control cell division and promote tumor development.

Impact of Splicing Defects on Cancer Development

Loss of splicing specificity can generate aberrant mRNAs that produce nonfunctional or harmful proteins, including defective tumor suppressors. This can lead to reduced tumor-suppressor activity, allowing cells to evade growth controls and accumulate mutations, thereby contributing to cancer progression.