Summary of - Moonlighting functions of the ubiquitin-like protein, Hub1/UBL-5

Document Type

Article

Abstract

Background: The faithful splicing of pre-mRNA is critical for accurate gene expression. Dysregulation of pre-mRNA splicing has been associated with several human diseases including cancer. The ubiquitin-like protein Hub1/UBL5 binds to the substrates non-covalently and promotes pre-mRNA splicing. UBL5 promotes the common fragile sites (CFS) stability and the Fanconi anemia pathway of DNA damage repair, which also suggests that UBL5 might be implicated in cancers. Therefore, we analyzed the UBL5 expression in TCGA tumor sample datasets and observed the differences between tumor and normal tissues among different tumor subtypes. We have noticed the alteration frequency of UBL5 in TCGA tumor samples. Altogether, this review summarizes the UBL5 functions and discusses its putative role in tumorigenesis.

Conclusion

Hub1/UBL5 is a small evolutionarily conserved multifaceted protein involved in various physiological processes of the cell. It is shown to promote splicing of only selected pre-mRNAs in S. cerevisiae, S. pombe, C. elegans, A. thaliana and human cell lines.

Recent studies suggest non-splicing functions of UBL5 such as UPRmt, FA DNA repair pathway and degradation of viral protein. These multifaceted actions could be attributed indirectly to its splicing function. However, to better understand these functions, generation of splicing-independent UBL5 mutant variants that disrupt the interaction with specific binding partners of particular pathways are to be identified.

In addition, Hub1 levels are fine-tuned under both normal and abnormal physiological conditions in the cells to regulate the splicing function critically. Alteration of its levels can have deleterious effects on the cell’s functioning.

References: Kolathur KK, Mallya S, Barve S, Bojja SL, Wagle MM. Moonlighting functions of the ubiquitin-like protein, Hub1/UBL-5. The international journal of biochemistry & cell biology. 2023 Sep;162:106445.

Publication Date

2023

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