Abstract
The Rho family of GTPases consists of 20 members including RhoE. Here, we discover the existence of a short isoform of RhoE designated as RhoEα, the first Rho GTPase isoform generated from alternative translation. Translation of this new isoform is initiated from an alternative start site downstream of and in-frame with the coding region of the canonical RhoE. RhoEα exhibits a similar subcellular distribution while its protein stability is higher than RhoE. RhoEα contains binding capability to RhoE effectors ROCK1, p190RhoGAP and Syx. The distinct transcriptomes of cells with the expression of RhoE and RhoEα, respectively, are demonstrated. The data propose distinctive and overlapping biological functions of RhoEα compared to RhoE. In conclusion, this study reveals a new Rho GTPase isoform generated from alternative translation. The discovery provides a new scope of understanding the versatile functions of small GTPases and underlines the complexity and diverse roles of small GTPases.
Highlights
The Rho family of GTPases consists of 20 members including RhoE
While new isoforms derived from alternative splicing were identified in Rho GTPase family before[25,26], we report here that RhoEα is the first Rho GTPase isoform generated from alternative translation, demonstrating the diversity of the GTPase family
The two immunoblot protein bands were detected in HeLa, HEK293, and mouse embryonic fibroblast (MEF) cells as well (Fig. 1b), and their expression levels can be decreased by the treatment of siRNA specific for RhoE in these cells (Fig. 1b)
Summary
We discover the existence of a short isoform of RhoE designated as RhoEα, the first Rho GTPase isoform generated from alternative translation. While the regulatory roles of RhoE have been almost entirely linked to cell actin cytoskeleton dynamics, cell migration, and apoptosis in its early studies[9,10,11,12,13], we have uncovered versatile functions of RhoE in intracellular Ca2+ homeostasis regulation[14], apoptosis[15], angiogenesis[16], inflammation[17], brain development[18], and glioblastoma genesis[19,20] along with other groups[21,22,23,24]. The study opens a new perspective for future studies in the exploration of Rho GTPase multiplicity and the interpretation of their diverse functions
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