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Comments on Zhang, H et al. (2013) International Worm Meeting "Dynamic interaction between hemidesmosomes and actin cytoskeleton regulated by RNA alternative splicing in elongating C.elegans epidermis." (0)
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Zhang, H, Fu, R, Zahreddine, H, & Labouesse, M (2013). Dynamic interaction between hemidesmosomes and actin cytoskeleton regulated by RNA alternative splicing in elongating C.elegans epidermis presented in International Worm Meeting. Unpublished information; cite only with author permission.
C.elegans hemidesmosomes (CeHDs) share similar structure and composition with their mammalian counterparts, making C. elegans an ideal model for studying hemidesmosomes. Despite its importance, how the dynamics of hemidesmosomes are regulated at the mRNA level is poorly understood. Here we focus on the role of transcription factor lst-3, identified in a previous screen searching for VAB-10A enhancers, in CeHD biogenesis. Loss of LST-3 function in a vab-10(e698) background resulted in CeHD disruption and muscle detachment from the epidermis. Quantitative RT-PCR data showed that the transcription levels of the CeHD-related genes were unchanged upon loss of LST-3 function. However, the alternative splicing of exon 17 in unc-52, the predicted basement ECM ligand of CeHDs, was particularly enhanced. Expression analysis further revealed that the mRNA level of splicing factor SMU-2 was upregulated in lst-3 mutants. Overexpression of SMU-2 in embryos resulted in increased amount of the UNC-52 isoform with exon 17, as well as CeHD disruption and embryonic lethality siminar as what caused by lst-3 loss of function. It suggests that LST-3 may regulate CeHD biogenesis mainly through repressing smu-2 expression. To further explore the mechanisms of alternative splicing on CeHD biogenesis, we examined the CeHD pattern as relative to the circumferential actin bundles (CFBs) in the epidermis. In wildtype situation, newly formed CeHD stripes and CFBs are positioned in a perfectly alternating fashion. During late elongation, however, the CeHD stripes and actin bundles gradually close in upon each other and eventually overlap. Interestingly, in mutants with elevated UNC-52 isoform with exon-17, there are significantly more overlapped CeHD /CFBs compared to the wildtype situation. On the other hand, in unc-52(e669) mutants that are devoid of UNC-52 isoform with exon-17, the phenotype was reversed. These results further suggested the constant crosstalk between the CeHDs and the actin bundles during epidermal elongation, and the active roles of alternative splicing in regulating such crosstalk.
Affiliations:
- IBMS, Soochow University, Suzhou, Jiangsu, China
- IGBMC,Strasbourg, France