Genetic Compensation Response in CRISPR-Based Gene Function Studies
6. Validation Across Multiple Models
Verifying gene functions in different species or cell lines helps distinguish between redundancy and specificity. Studies on organisms or cell lines with fewer homologous genes can reduce the impact of GCR, revealing clearer phenotypic outcomes.
Conclusion and Future Perspectives
Research on genetic compensation responses highlights the complexity of gene function and redundancy while introducing both challenges and opportunities for CRISPR studies. To better dissect gene functions, researchers must account for GCR’s effects and adopt effective strategies to control or minimize its interference. By delving into the mechanisms underlying GCR and applying these mitigation techniques, we can reliably analyze gene functions and uncover new avenues for therapeutic development.
Moreover, GCR serves not only as a safeguard for genetic robustness but also as a potential driver of tumor progression. Understanding GCR’s role in diseases such as cancer could reveal novel therapeutic targets and strategies. Future studies on GCR will undoubtedly deepen our understanding of gene regulation and its implications for both health and disease.
Reference
- Ma et al., PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components. Nature. 2019 Apr;568(7751):259-263. doi: 10.1038/s41586-019-1057-y.
- Xie et al., Upf3a but not Upf1 mediates the genetic compensation response induced by leg1 deleterious mutations in an H3K4me3-independent manner. Cell Discov. 2023 Jun 27;9(1):63. doi: 10.1038/s41421-023-00550-2.
- Xu et al., Genetic compensation response could exist in colorectal cancer: UPF3A upregulates the oncogenic homologue gene SRSF3 expression corresponding to SRSF6 to promote colorectal cancer metastasis. J Gastroenterol Hepatol. 2023 Apr;38(4):634-647. doi: 10.1111/jgh.16152.